Eugene Friedman
- Medical Instructor in the Department of Medicine
https://medicine.duke.edu/faculty/eugene-friedman
A retrospective study of forty-six cases of herpes Laothamatas J gastritis juicing recipes purchase prevacid from india, Hemachudha T gastritis zeluca buy cheap prevacid 30 mg online, Mitrabhakdi E et al gastritis smoking cheap prevacid 15 mg overnight delivery. The neuropathology of Western equine and Kieburtz K gastritis vitamin c best prevacid 15 mg, Simpson D gastritis diet juicing 15mg prevacid for sale, Yiannoutsos C et al hemorrhagic gastritis definition proven prevacid 30mg. Rapid diagnosis of tuberculous antibiotic treatment in patients with persistent symptoms and meningitis by polymerase chain reaction assay of a history of Lyme disease. Histopathological central nervous system by Treponema pallidum: implications findings in the central and peripheral nervous system in for diagnosis and treatment. Cerebellar ataxia and infections reported in Japan between January 1979 and June central nervous system Whipple disease. Varicella zoster-associated neurologic disease encephalomyelitis presenting as an acute psychotic state. Varicella-zoster dementia complex as the presenting or sole manifestation of encephalomyelitis. Toxoplasmosis of the central nervous and sequelar epilepsy: first matched case-control study in system in the acquired immunodeficiency syndrome. A patient with cerebral panencephalitis: clinical and magnetic resonance imaging Whipple disease with gastric involvement but not evaluation of 36 patients. Chronic encephalitis possibly leukoencephalopathy: a complication of immunosuppressive due to herpes simplex virus: two cases. Delayed resolution of white Sanchez-Portocarrero J, Perez-Cecilia E, Jimenez-Escrig A et al. Subacute sclerosing panencephalitis: serial system: clinicopathological analysis of 17 patients. A double-blind trial in encephalitis: pathological confirmation of viral reactivation. Evaluation of patients amitriptyline in postherpetic neuralgia: a randomized trial. Progressive multifocal anatomically by deposits of fat and fatty acids in the leukoencephalopathy presenting as human immunodeficiency intestinal and mesenteric lymphatic tissues. Inherited cases tend to appear a bit earlier, mostly may become abnormal only as the disease progresses, and in the early fifties. Most importantly, the 14-3-3 ease has been described in several studies (Brown et al. With progression almost all patients Course become profoundly demented, and the dementia is accompanied by myoclonus (which may be stimulus responsive) this disease progresses rapidly, with death occurring within in almost 90 percent of cases. The finding of prions within the olfactory neusurviving for up to 3 years (Masters and Richardson 1978; roepithelium is intriguing in this regard, as their presence Pocchiara et al. The within the gray matter of the cerebral cortex, basal ganglia, pathologic prion protein actually exists in two isoforms, thalamus, and cerebellar cortex (Masters and Richardson type 1 and type 2, and in each patient it appears that only 1978), which in turn is accounted for by grossly swollen one type is present. There is also neuronal loss and how useful this classification scheme is for clinical work. It is a constituent of the neuronal cell membrane and via the following procedures: corneal transplants (Duffy et al. Eventually, with an accumulation of which the dura mater remained extracranial (Antoine et al. The persistence of prions cannot be overemphasized: As an aside, in the literature the normal form of the in one case (Gibbs et al. In addition to this pulvinar sign, increased signal intensity may also occur in the basal ganglia Treatment and the cerebral and cerebellar cortices (Collie et al. To date, the only medication shown to have any speperiodic spike-and-slow-wave complexes are absent (Zeidler cific usefulness in a double-blind study is flupirtine, which et al. Early uncon14-3-3 protein is found in about 50 percent of cases (Green trolled reports suggested a usefulness for amanatadine et al. The question inevitably arises as to what sorts of precauCourse tions should be in place to guard against transmission of the disease. Although isolation does not appear to be necessary, the disease is relentlessly progressive, with most patients routine universal precautions are appropriate. In cases of accidental contact, consideration Etiology may be given to washing with a 1:10 solution of 5 percent common hypochlorite bleach, which is effective. Host factors appear to play a role in susceptibility among humans in that, with Course rare exceptions (Ironside et al. Within the thalamus, basal ganglia, and also the cerebral and cerebellar cortices there are widespread prion Etiology plaques surrounded by spongiform change (Will et al. It also appears that prions are present in Mutations have been noted at codons 102 (Arata et al. As noted here, the pulvinar sign amyloid plaques that stain positively for prion proteins is quite important, but it must be borne in mind that it is not (Kitamoto et al. Although the distribution of these microscopic changes varies, the cerebellar cortex, basal ganglia, and cerebral cortex are generally involved. Strenuous efforts the differential diagnosis of dementia occurring in the are in place to prevent bovine spongiform encephalopathy; context of ataxia is discussed in Section 5. Fatal familial insomnia is a rare prion disease, characterized, as the name suggests, by severe insomnia, which is Clinical features typically accompanied by a dementia and prominent autonomic disturbances. The onset is subacute or gradual, and usually in the sixth decade, with a wide range from the third to the eighth decades. Clinical features 1989), patients present with a progressive ataxia with the eventual development of a dementia; in some cases Onset is typically subacute or gradual and occurs in middle parkinsonism or long-tract signs may also occur. Paroxysms of autonomic disturbance often occur, with hyperhidrosis, tachycardia, hypertension, and irregular respiration. Importantly, although insomKuru is a unique human prion disease, spread by cannibalnia is the initial hallmark of this disease, in some cases it ism and present only in the Fore people of New Guinea may appear late in the course and, rarely, it may be absent (Gajdusek 1977). Clinical features Course After a long incubation period, spanning from 4 to 50 years or more (Collinge et al. Pathologically (Gajdusek and bral and cerebellar cortices and in the dorsal raphe and Zigas 1959; Kakulas et al. It also appears that the same clinical and neuropathologic picture may Differential diagnosis occur on a sporadic basis (Parchi et al. The diagnosis is only relevant in those Fore tribespeople who engaged in cannibalism. Differential diagnosis the diagnosis is typically suspected in cases marked by Treatment intractable insomnia. Severe depression in the elderly may be marked by dementia and by insomnia, but in such cases There is no known treatment. Fatal familial insomnia: cerebrospinal fluid as a marker for transmissible spongiform a second kindred with mutation of prion protein gene at encephalopathies. Anxiety commonly accompanies the depression prednisone) or endogenous overproduction of steroids. Both suicide attempts and completed suicides turn exerts a negative feedback effect on the hypothalamus may occur (Jeffcoate et al. Cases due to exogenous steroid use Dementia is likewise rare and is often characterized by are of the most rapid onset, and may appear within days. All of internal jugular blood and systemic venous blood will not these features, however, take time to develop and thus may be present.
For evaluating epileptic foci gastritis diet generic 15 mg prevacid with visa, the reference is nor(isopotential with the reference) measure a negativity at input mally chosen to be completely uninvolved in the electrical 1 equal to that at the reference gastritis symptoms last cheap prevacid american express. If the recorded potential has field distribution of the spike or sharp wave (all deflections two maxima of opposite polarity gastritis symptoms in infants discount prevacid 30 mg, such as seen in tangential should point in the same direction) gastritis diet drinks purchase prevacid 30mg on line. Typically gastritis eating out purchase prevacid with a visa, the electrode dipole sources gastritis diet and treatment generic prevacid 15mg fast delivery, then referential montages will show phase most distant from the activity of interest will be the least reversals even if the reference is the minimum. An elecChoice of a Reference trode at the vertex (Cz) is an excellent reference for displaying temporal spikes but may be a poor choice during sleep In a referential montage, any electrode may be the reference, when it is very active. In the linked-ears reference (88) (frebut ordinarily it is the one uninvolved in the electrical field. This electrical shunt changes the field genering the voltage measured referentially at electrode B from ated (89), decreasing, for example, asymmetries between the that measured referentially at electrode A will produce temporal regions (9) and producing other distortions (90). This is true for a sindepend entirely on the electrode impedances, with the ear gle electrode or a mathematically calculated one such as the having the lower impedance predominating. When temporal Chapter 7: Localization and Field Determination in Electroencephalography 85 lobe epileptiform activity spreads to the ipsilateral ear, the linked-ear reference will inappropriately reveal spikes in both hemispheres. The disadvantages of this system are threefold: (i) the common average reference is, by definition, contaminated because the abnormal potential will influence all of the channels (91); (ii) depending on the number of electrodes included in the average, the potential under study will be reduced by a small proportion; and (iii) largeamplitude focal pathologic activities will be reflected proportionally in all the inactive channels as well, albeit with apparently opposite polarity. A variety of calculated references and transformations are available, but these must be used with caution. Because there is no ideal reference for all cases, it is usually best to distribute the electrical field potentials by manual selection of an uninvolved and quiet electrode as a reference. Assumptions After determination of the electrical field, the sources respondownward deflection with no phase reversals may be genersible for the production of the field can be localized with the ated by either a negativity maximum at the last electrode of aid of a number of simplifications. To choose between the two possibilities in the following four specific assumptions: any given case, one must guess about the polarity of the source 1. Epileptogenic sources are simple dipoles or sheets of generator or the relative likelihood of one of the two elecdipoles obeying a simple principle of superposition (46). Dipoles are fundamentally oriented perpendicularly, with Because the localization of a transient will depend on a only one pole generally detectable on the scalp (75), and correct assumption about its polarity, all possible clues must therefore can be treated as if they were monopoles. For examboth the positive and the negative poles are recorded from ple, if the transient appears to be epileptiform, it is most the surface, the localization system outlined below will likely to be surface negative, whereas if morphology and not apply. Epileptiform discharges are chiefly surface-negative pheit can be expected to be surface positive. In the absence of a skull defect, a transversestrategy is to see if the distribution based on the assumed lying dipole (as in benign focal epileptiform discharges of polarity makes physiologic sense; if not, the opposite polarity childhood), or other evidence of an unusual discharge, will have to be tried. The head is essentially a uniform, homogeneous volume activity than the opposite assumption. Determination of the electrical field of a discharge may help Choosing Between Two Possibilities to differentiate artifacts or extracortical physiologic activity from abnormal brain activity. Because the electrical the application of the rules above will yield two possible gradient is steepest at the electrodes closest to the source, the hypotheses in each case. If the electroencephalographer assumed instead that they were negative, suggesting epileptiform discharges, their distribution across the entire head would have been more difficult to explain physiologically. For this reason, the steepest potential gradient, and the largest deflection, will most often appear in the channels nearest the source. When dealing with an invariant spike, seen in various chains and montages, analyses based on any of the multiple electrode chains or montages should all reach the same conclusion (see. Corroborating a potential localized on a longitudinal montage by using a transverse montage. If different conclusions result from the analysis of different montages, the assumptions about polarity or location were probably incorrect on one of the montages. Nevertheless, consistent conclusions across montages do not prove that the assumptions were correct, as the same error about polarity or location may have been made throughout the analysis. The sharply contoured discharges emanating from the left posterior region cannot be dismissed as artifacts on the they presuppose a single monopolar generator. However, since they appear only in channels 4 and 12, they frequently satisfy this assumption as an approximation. Because the field shows a preciptors of the same or different polarity acting simultaneously. On the right, an ad hoc distribution montage employing a contralateral electrode clearly shows a typical centro-temporal distribution. It is also easier to distiguish the eye movement artifacts from the sharp waves in this montage. This mistake is most likely to occur when the chain sent by definition, one of them is oriented deep within the head, has no phase reversals, indicating that the maximum of the allowing assumption of a monopole. On occasion, however, discharge originates from either the beginning or the end of both poles may be represented on the scalp surface, precluding the chain or when the maximum is broadly distributed across the use of these rules. A greater amplitude seen in one an epileptogenic focus originating from the superior mesial or more channels is solely a manifestation of a greater potenportion of the motor strip (95). Multiple fast Specifically, the end of the dipole traditionally at the surface components may be confusingly mixed when viewed from a will be buried within the fissure with its maximum seen on the bipolar montage and are more accurately represented in a refcontralateral scalp, and the ordinarily deep end of the dipole erential montage to identify the individual components that may be close to the scalp surface on the ipsilateral side. A discharge with an of their location, horizontal dipoles also can be seen in benign extremely broad field can result in rather tiny differences focal epileptiform discharges of childhood (96). The electrical fields resulting from these transverse dipoles Because the brain, skull, and scalp do not have homogeare characterized by a simultaneous surface-negative and surneous conductivity, current pathways from active epileptoface-positive potential seen at different electrodes on the scalp genic areas can vary dramatically among the recording sites. Note that when doublethis variability may lead to a site of maximal scalp activity phase reversals or other factors indicate, for example, a huge considerably distant from the fundamental generator (98). A horizontal dipole particular set of measurements often will have to be based on should not be the first thought when the electroencephalograexperience and information that is not easily derivable from pher confronts deflections pointing in opposite directions. Nevertheless, by remaining aware of alternainvolved reference, the most common cause for this phenometive possibilities, the electroencephalographer can avoid misnon, must be excluded. The phase reversal of this arciform activity spans the isoelectric channels, consistent with the broad distribution of a wicket rhythm. Computer-aided mapping can accurately summarize the field distribution and may help to highlight locally originating activity (99). Computed topographic maps can be used (i) to describe an already known localization (perhaps for communication with non-neurophysiologists), (ii) to confirm a conventionally determined localization, (iii) to identify changes not detected in the original interpretation, and (iv) to display statistical differences between patient populations (so-called Z scores) (100). Automated mapping may be used to represent the topographic distribution of any variable, whether derived from complex calculations or simply displaying electrical field distributions as shown in Figure 7. Digtization of the electroendistribution of sharp waves may present a valuable display, cephalogram offers the opportunity for interactive postprocessing that may help to convey location in an easy to understand way. Using baseline-to-peak amplitude measurehave been done manually, so that visual inspection of the ments from a Cz reference, interpolating the amplitudes at every scalp waveform is essential for each map (101). Chapter 7: Localization and Field Determination in Electroencephalography 89 only 16 to 32 points, with the balance obtained via interpolafact that the amplitude seen on the scalp is a function of not tion, creating the illusion of a higher resolution than actually only its distance from the generator but also the orientation of exists. As a result of volume conduction, potentials tionship between scalp potentials and the underlying cortical generated within a small brain region will be seen over a wide generators is the nonhomogeneity of the cerebral tissue, scalp, area of scalp. These spatial deblurring techniques such as the tion that attempt to address some of these difficulties. Computerized source analysis is an attempt to taking into account the direction of the field along the scalp to identify the origin of electrical potentials seen on the scalp by define the differences between adjacent electrodes. In There are a number of pitfalls and caveats associated with order to explain a widespread scalp distribution, the computer topographic mapping (108,109) that have prevented widemodel tends to locate these dipoles deep to the actual cortical spread acceptance of this technique for most clinical applicalocation. Because not all the channels may be at positions of the electrical sources in the brain from the scalp their peak simultaneously, the maps may show an unexelectrodes (122), appropriate assumptions can yield useful pected result, that is, the maps may demonstrate spike proinformation in some cases (16,123). An illustration of the gression but will not necessarily reflect the manually deterpractical use of the equivalent current source dipole method to mined localization (110). Moreover, computer topographic localize an epileptic discharge is shown in Figure 7. Topographic In recent years, purveyors of these packages have enhanced mapping techniques, even with sophisticated enhancements their offerings to be of more use in clinical medicine. Several such as the Laplacian operator or spatial deblurring, do not journals have dedicated special issues to the various aspects of provide any conclusive three-dimensional information about this methodology (126). This software methodology is sometimes limited, decrease errors, several restrictions imposed by the interpolabecause in clinical use only the simplest of models of the tion methods and the boundary value problem dictate the source. The temporal dynamics of the Indeed, adding closely spaced electrodes alone may reveal source and the intracranial anatomic pathology associated new information. There are, however, difficulties in identifythe sensors is especially complex for the electroencephalograing the source of a scalp potential that derive, in part, from the phy of patients with highly distorted head anatomy. Spontaneous and convulsoid While new imaging techniques have decreased the imporactivity. Clinical ictal patterns in epileptic patients with occipital electroencephalographic foci. Occipitotemporal epilepsy studied with stereotaxically implanted depth electrodes and successfully treated by 1. Electrical Fields of cephalography: application of volume conductor theory to electroenthe Brain. J Clin stantially the distribution of extracranial electrical fields in an in vitro Neurophysiol. Design and evolution of a system for long-term electroendipolar sources for temporal spikes in presurgical candidates. Localization of epileptogenic spike foci: comparative study of drug resistant partial epilepsy: patterns of conduction and results from closely spaced scalp electrodes, nasopharyngeal, sphenoidal, subdural, and dipole reconstructions. Commentary: chronic intracranial recordplex epilepsy: comparison between dipole modeling and brain distributed ing and stimulation with subdural electrodes. Temporal epileptogenesis: localizing cal and scalp activity using chronically indwelling electrodes in man. Paradoxical lateralization of the evaluation of patients with intractable epilepsy. Precautions in topographic mapmultiple basal electrodes, I: description of method. Ten percent electrode system for topoin the topographic analysis of brain electrical activity. Spherical splines for scalp potential the sphenoidal electrode accurately identify a mesio-temporal epileptogenic and current density mapping. Source derivation recordings of generalized spikeNiedermeyer E, Lopes da Silva F, eds. Surface mapping of spike potential sis of rolandic discharges in benign childhood epilepsy. Multiple source analysis of interictal spikes: goals, epilepsy using magnetic and electric measurements. Standard activation procedures such as hyperventilation and photic stimulation should be included. Rationale Adequate levels of sleep may be attained after administration of chloral hydrate. However, in patients with very frequent paroxysground for age is critical to appropriate interpretation. Nonspecific changes, such as generalized or focal slowization of the epileptogenic region (9). Supraorbital electrodes, wave activity and amplitude asymmetries, are not unique to which record from the orbitofrontal region, may be useful in epilepsy and do not indicate an increased epileptogenic potenpatients with partial epilepsy of frontal lobe origin (2). Interictal epileptiform alterations with which interpretable ictal recordings may be obtained identify the irritative zone that may mark the epileptic brain over paper recordings. Potentially epileptogenic activity may be attenuated by dura, the main types of epileptiform discharges are spikes and bone, and scalp, or degraded by muscle artifacts (1). Therefore, sharp waves, occurring either as single potentials or with an epileptiform activity generated in cortex remote from the surafter-following slow wave, known as a spike-wave complex. Rarely, the periodic complexes can be more difcance as temporal lobe spike or sharp-wave discharges (5). An aura preceding impairment of contriphasic waves (5), although complexes of repetitive discharges sciousness may be without obvious electrographic accompanialso may be seen (29). The temporal lobe has the lowest threshdiagnosis of nonepileptic clinical behavior. Focal epileptiform Temporal Lobe Epilepsy discharges may occur over any location on the scalp and depend on the age of the individual and the site of the pathoTemporal spikes are highly epileptogenic and represent the logic lesion. The spike discharge amplitude is maximal Epileptiform discharges may appear to be generalized or multiover the anterior temporal region (in contrast to the cenregional (hypsarrhythmia) even in the presence of a focal brain trotemporal spike) and may prominently involve the ear leads. Chapter 8: Application of Electroencephalography in the Diagnosis of Epilepsy 97 lateralized moderateto high-amplitude rhythmic paroxysm of activity is most prominent in the temporal scalp electrodes and may progress to generalized rhythmic slowing maximal on the side of seizure onset. Focal temporal lobe or generalized arrhythmic slow-wave activity may occur postictally. Interictal temporal lobe spiking may increase at the termination of the seizure (35). Sphenoidal and inferolateral temporal scalp (T1, T2, F9, F10) electrodes, as well as closely placed scalp electrodes, can be useful in delineating the topography of the interictal activity (2,4,22,23,33).
A randomized gastritis diet order prevacid visa, placeboand low amyloid beta-42 levels in the clinical diagnosis of controlled comparative trial of gabapentin and propranolol in Alzheimer disease and relation to apolipoprotein E genotype gastritis diet proven 30 mg prevacid. Progression of repeat and phenotypic variability of spinocerebellar ataxia abnormalities in adrenomyeloneuropathy and neurologically type I chronic atrophic gastritis definition discount 15 mg prevacid free shipping. Dentatorubropallidoluysian diffuse cortical Lewy body disease (Lewy body dementia) gastritis remedies buy prevacid 15mg on-line. Donepezil therapy in to persons with the fragile X associated tremor/ataxia clinical practice stomach ulcer gastritis symptoms buy prevacid 15 mg with visa. Alzheimer disease leukodystrophy: clinical gastritis symptoms tongue cheap prevacid 30mg on line, biochemical, and neuropathologic and nonfluent progressive aphasia. Double-blind, placebo controlled phosphorylated tau epitopes in the differential diagnosis of trial of botulinum toxin injection for the treatment of Alzheimer disease: a comparative cerebrospinal fluid study. Hypersomnia associated with alveolar hypoAdrenomyeloneuropathy: a probable variant of ventilation in myotonic dystrophy. Neuroacanthocytosis: a examination of a large family and discussion of other clinical, haematological and pathological study of 19 cases. Lessons from a parkinsonism, and generalized brain atrophy in male carriers remarkable family with dopa-responsive dystonia. Med Surg Reporter Philadelphia 1872; clinicopathological study of three Dutch families. Corticobasal degeneration with between depression and loss of neurons in the locus primary progressive aphasia and accentuated cortical lesion in coeruleus in Alzheimer disease. Amitriptyline in the management of progressive characteristics of progressive aphasia. Frontotemporal dementia: metachromatic leukodystrophy by bone marrow a randomized, controlled trial with trazodone. J Neurol Neurosurg Psychiatry Behavioral, cardiovascular, and neurochemical effects. Accuracy of the clinical diagnosis correlative neuropathology using anti-ubiquitin of corticobasal degeneration: a clinicopathologic study. Idiopathic torsion dystonia (dystonia excessive somnolence and enhances mood in patients with musculorum deformans): a review of forty-two patients. Characterization of the dementia with Lewy bodies: a randomized, double-blind, pattern of cognitive impairment in myotonic dystrophy type 1. Clinical characteristics of the xanthomatosis: the storage of cholestanol within the nervous geste antagoniste in cervical dystonia. Cognitive and motor dystonia: the spectrum of clinical manifestations in a large assessment in autopsy-proven corticobasal degeneration. Frontotemporal lobar tremor: a multiple-dose, double-blind, placebo-controlled degeneration: a consensus on clinical diagnostic criteria. Dentatorubralquantitative immunohistochemical study and relation to pallidoluysian atrophy. Autosomal dominant adult Gilles de la Tourette syndrome: a 5-week double-blind crosscerebral neuronal ceroid lipofuscinosis: parkinsonism due to over study vs. Low-dose clozapine for the treatment of Pierantozzi M, Pietrousti A, Brusa L et al. Late-onset metachromatic clinical findings in a family with dentatorubral-pallidoluysian leukodystrophy. Electron microscopic structure of the pathological and biochemical observations in a case. Essential tremor course and myopathy: a new dominant disorder with myotonia, muscle disability. Proximal myotonic Lewy bodies according to the consensus criteria in a general myopathy: clinical features of a multisystem disorder similar population aged 75 or older. J Neurol Neurosurg Psychiatry 2005; dementia with Lewy bodies: worsening with memantine. Mental deficiency associated with antibody titers and anti-basal ganglia antibodies in patients muscular dystrophy: a neuropathological study. J Neurol Neurosurg Psychiatry Hyperekplexia: a syndrome of pathological startle responses. A clinical and pathological study of 17 replacement therapy and the risk of Alzheimer disease. A clinical, morphological, haloperidol, pimozide, and placebo for the treatment of Gilles biochemical and immunological study. Characteristics of the transmitted focal dystonia in families of patients with dementia in late-onset metachromatic leukodystrophy. Long-term effect of bonedegeneration: neuropathologic and clinical heterogeneity. Fatal hyperpyrexia after withdrawal human putamen in children with Tourette syndrome.
Toriello a careful physical examination gastritis honey discount 30mg prevacid overnight delivery, including documentation of dysmorphic features as well as the behavioral phenotype; chromosome analysis gastritis vagus nerve discount 15 mg prevacid visa, consideration of testing for fragile X gastritis diet salad buy prevacid 15 mg low price, citing a 2% yield in the studies they reviewed; metabolic testing under suggestive circumstances; and intracranial imaging gastritis symptoms spanish purchase prevacid 15 mg with mastercard. However gastritis diet virus buy generic prevacid pills, in certain situations (such as consanguinity gastritis diet 24 order 15mg prevacid with amex, isolated population) or if clinically indicated, the yield increases to 5%. Finally, the American Academy of Pediatrics [9] published their recommendations in 2006, which were similar to those made by other groups. This group also stressed the importance of the dysmorphologic exam, as well as the neurologic exam in the diagnostic approach. In many cases, the dysmorphologic exam was sufficient to establish the diagnosis, whereas the neurologic exam was useful in determining the need for further studies or referral to other specialists. Metabolic studies have a similarly low yield of 1%, but here routine screening is not recommended. Instead, metabolic studies should be done on the basis of clinical findings in the patient. As a result of the widespread use of this technique, a few microdeletions or microduplications have been found to be particularly common. These features include upslanting, widely spaced eyes, prominent philtrum, and full everted lips. The hands may also show minor anomalies, including clinodactyly or short fourth metacarpals [14]. Autism spectrum disorders are also fairly common in those with this microdeletion, having been reported in at least 20%, depending on the mode of ascertainment [15]. These are rather variable, but can include fiat facial profile, hypertelorism, and smooth philtrum. Recently, it has been reported that obesity or overweight are relatively more common in individuals with this deletion who are more than 4 years of age, becoming a constant manifestation in those in their teens or older [16]. Phenotypic manifestations include low birth weight, severe neonatal hypotonia, poor feeding, and a dysmorphic facial appearance, which includes a long face, blepharoptosis, so-called pear-shaped nose, broad chin, and apparently low-set ears. None of these conditions had been recognized prior to the institution of microarrays in the diagnostic repertoire, and it is expected that more relatively common microdeletion or microduplication syndromes will be described over time. A well-known example of this is the association of Williams syndrome with the deletion of 7q11. In this situation, there have been one or more reports in the literature, but there is a less consistent phenotype among the various reports. Marker chromosomes may also be missed, depending on the size, marker composition, and array coverage of the specific chromosomal area [21]. Detection of mosaicism has been reported, but the accuracy of detecting low levels described by some groups has been questioned by others [19, 21]. However, it may be reasonable to screen for creatine deficiency disorders, which are relatively common and may be treatable, and congenital disorders of glycosylation, because regression (a hallmark of metabolic disorders) is often not present [2, 22]. Coupled with microarray analysis and testing for trinucleotide repeat expansion conditions. Diagnostic yield of the comprehensive assessment of developmental delay/mental retardation in an Institute of child Neuropsychiatry. Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, Zenker M, Huffmeier U, Thiel C, Ruschendorf F, Nurnberg P, Reis A, Trautmann U. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness. High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Analytical and clinical validity of wholegenome oligonucleotide array comparative genomic hybridization for pediatric patients with mental retardation and developmental delay. Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. A new chromosome X exon-specific microarray platform for screening of patients with X-linked disorders. Toriello Abstract Numerous genetic syndromes have had the cognitive and behavioral components of the phenotype delineated, leading to improved diagnosis of the condition, as well as to better management and interventional approaches. This article is a review of some of what is known about the neurodevelopmental aspects of some of the more common genetic syndromes. Introduction Although the cognitive aspects of various syndromes have been recognized for years, more recently clinical geneticists and others have come to recognize the importance of delineating the behavioral profile as well. As defined by some, the behavioral phenotype encompasses motor, cognitive, communicative, and social aspects of the specific condition under study [1]. From a diagnostic standpoint, the behavioral phenotype may be as, if not more, important than clinical features in terms of recognizing the syndrome. Additional information that can be gained from studying cognitive and behavioral phenotypes of individuals with syndromes is that we gain an understanding of genetic infiuences on brain function, which can then be applied to both research and intervention [2, 3]. The following is a summary of what is known about the neurodevelopmental aspects of a number of genetic syndromes. This is not meant to be an exhaustive list but to provide insight into what we know about some of these conditions. A unique behavioral profile is part of this phenotype and is characterized by (inappropriate) happy disposition with frequent laughter, often accompanied by hand fiapping. However, there were differences among the different adaptive behaviors that were measured, with motor skills most impaired and socialization least impaired [4]. Speech impairment is generally considered to be severe, with none or limited use of words, although receptive speech is better than expressive speech [5]. Relatively consistent behaviors include frequent laughter or smiling, excitability. Additionally reported behaviors include feeding problems, fixation on food, hyperphagia, and increased heat sensitivity. The laughter, which is thought to be pathognomonic, has been further studied to determine the context in which it occurs. It was initially thought to be unprovoked and to occur inappropriately; more recently it has been suggested to be related to context, although it may occur in situations that are not considered to be pleasant. It may also increase during periods of anxiety; however, in general it does appear to occur more frequently in social situations and less in nonsocial situations [1]. The cognitive deficits can be characterized as deficiencies in learning, memory, and language, with morphosyntax, verbal shortterm memory, and explicit long-term memory usually impaired, and visuospatial short-term memory, associative learning, and implicit long-term memory usually preserved [8]. Since praxis is involved in many skills of everyday living, it was not surprising that a correlation between praxis skills and function on the daily living skills domain of the Vineland Adaptive Behavior Scales was found. As a result of finding a specific profile of praxis deficits, the authors recommended that this information be used for intervention planning by occupational therapists and other practitioners. The latter two conditions manifest as noncompliance, disobedience, or aggressive behavior. Conversely, older adults have also been well characterized, given the significant frequency of dementia in this group. However, Adams and Oliver [11] found that behavioral changes were more common in those with cognitive decline, as evidenced by a number of neuropsychological tests. Fragile X Syndrome Fragile X syndrome is considered to be the most common cause of inherited cognitive impairment. The physical phenotype is fairly subtle, with males generally having a long face, large and/or protruding ears, average to large head size, and after puberty, macroorchidism. Above 200 repeats, the gene is considered fully mutated, and as a result, fully methylated (shut off) and not expressed. Both males and females can have premutations or full mutations, with the effect determined by their genetic status. The mutation can be present in every cell or only in some cells (in which case the individual is said to be mosaic). Males with the full mutation have been described as having a characteristic cognitive and behavioral phenotype. However, strengths include vocabulary, verbal working memory, and long-term memory for meaningful and learned information [13]. However, both males (and females) with fragile X can also exhibit hyperactivity, 6 Neurodevelopmental Disorders in Common Syndromes 83 impulsivity, tantrums, aggression, destructiveness, and self-injurious behavior [15]. Females with the full mutation can have significant cognitive impairment, but this is related to the pattern of X inactivation (remember, in females, one of the X chromosomes becomes inactivated during embryogenesis). Furthermore, women with a full mutation whose cognition falls within the normal range are still more likely to have executive function deficits and some behavioral differences. These include greater deficits in socialization, and being rated as withdrawn or depressed more often than controls [18]. Females with a premutation do not have any discernible executive function problems; however, there is some evidence that these women are more likely to have social phobia, panic disorder and/or agoraphobia, and anxiety disorders [19]. It should not be surprising that women with a full mutation also exhibit impaired social interaction, as well as impulsivity, shyness, moodiness, and inattention [15]. It is not surprising therefore that language and speech impairments are also common, and are present at all ages. In the early school years, problems with reading, spelling, and writing (but not arithmetic skills) are common. In addition, these boys have difficulties with articulation, word finding, and phonemic processing. Toriello impaired reading, spelling, and arithmetic are prevalent, with most of these boys receiving special education. It has been known for some time that attention deficit is more common in these boys. Recently, however, in the group of 51 boys with Klinefelter syndrome mentioned above, Bruining et al. They emphasized that not only should there be awareness of the high frequency of psychopathology in these boys but also in any boy who is exhibiting behavioral problems, especially in conjunction with a nonverbal learning disability, a karyotype should be done. One study had found that during childhood, being shy, quiet, and underactive was not uncommon. However, as Visootsak and Graham [26] point out, many of these studies were done on males who were not receiving testosterone replacement therapy. This treatment has been shown to increase self-esteem and a feeling of wellbeing in this group of males. In addition, males diagnosed prenatally or at birth had fewer behavioral problems as compared to males who were diagnosed postnatally, likely because of anticipatory guidance in the former group. As a group, they are described as being immature, passive, and subject to temper tantrums and outbursts; however, they are less likely to have internalizing and externalizing maladaptive behavior. Both cognitive and behavioral functions are impaired in many individuals with this condition. The facial phenotype changes with age but in general consists of hypertelorism, ptosis, and prominent nasolabial folds [31]. Few studies have investigated cognitive and behavioral functions; however, the studies that have been done have found deficits in both. Cognitive impairment is virtually always present, as are characteristic behavioral abnormalities. In general, the degree of cognitive impairment is in the borderline to mild/moderate range. Similarities and differences were found between the two groups in terms of subtests. In both groups, vocabulary subtest was identified as a strength, whereas digit span, digit symbol, and digit symbol coding were found to be weaknesses. The nondeletion group had weakness in the picture arrangement subtest, whereas it had strengths in the information and similarity verbal subtests. Further evidence for distinctive genetic differences comes from the study by Whittington et al. In addition, those in the nondeletion group are also more likely to have psychosis (as many as 28% in some studies) and sleep disorders, whereas those with deletions are more likely to have skin picking, mood lability, food stealing, withdrawal, sulking, nail biting, hoarding, and overeating [39]. It has been shown that these behaviors increase with age, peaking in early adulthood. This is in contrast to the situation in those with cognitive impairment in general, whereby increases in psychiatric problems are found with increasing age [40]. The main manifestations include acquired microcephaly, loss of purposeful hand movements, and loss of communication and motor skills. However, adaptive behavior skills are slightly higher, with communication at a mean of 11 months, daily living skills at a mean of 14 months, and socialization at a mean of 10 months. These behaviors have been assigned to various domains, with these domains (and examples) including general mood (screaming spells, inconsolable crying, abrupt mood swings, and unexplained irritability); breathing problems (breath holding, swallowing air); hand behaviors (lack of purposeful grasp, difficulty stopping repetitive hand movements); repetitive facial movements (grimacing, tongue movements); body rocking and expressionless face; nighttime behaviors (spells of screaming or laughter during the night); fear/anxiety (apparent panic, holding parts of the body rigidly); walking, standing (walks with a stiff-legged gait, leans on objects when standing); other (appears isolated, hand wounds from repetitive hand movements). A recent study has shown differences in the behavioral phenotype based on the genotype. For example, those with the R294X mutation were more likely to have mood difficulties, body rocking, and nighttime behaviors, and less likely to have hand behaviors or repetitive facial movements.
A 4 year old with Hg poisoning developed an itchy gastritis diet ulcer cheap 30mg prevacid with visa, peeling rash on the extremities (Florentine and Sanfilippo gastritis webmd buy prevacid on line amex, 1991) gastritis symptoms loose stools prevacid 15 mg fast delivery. Mercury vapor inhalation caused a rash and peeling on the palms and soles of a pre-adolescent (Fagala and Wigg gastritis symptoms in hindi generic 15mg prevacid, 1992) gastritis hiv symptom cheap prevacid 30 mg on line. An acrodynia victim described himself as a child as having severe itching and a constant burning sensation at the extremities gastritis symptoms in elderly prevacid 15 mg with visa, resulting in him rubbing his hands and feet raw (Neville Recollection, Pink Disease Support Group). Acrodynia symptoms in an adult poisoned by ethylmercury injection included pink scaling palms and soles, flushed cheeks, and itching (Matheson et al, 1980). In acrodynia the skin may be rough and dry, and the soles and palms are usually but not necessarily red (Aronow and Fleischmann, 1976). Acrocyanosis is an uncommon disorder of poor circulation in which skin on the hands and feet turn red and blue; there is profuse sweating; and the fingers and toes are persistently cold (Carpenter and Morris, 1991). Sweating and circulatory abnormalities are also common in some forms of mercury poisoning. Acrodynia in adults and children results in excessive sweating, poor circulation, and rapid heart rate (Farnesworth, 1997; Matheson et al, 1980; Cloarec et al, 1995; Warkany and Hubbard, 1953). The 12 year old with mercury vapor poisoning sweated profusely, especially at night (Fagala and Wigg, 1992), and elevated blood pressure has been reported in exposed workers (Vroom and Greer, 1972). Autonomic system abnormalities can be caused by disturbances in acetylcholine levels, known to be deficient in both autism and Hg poisoning (see neurotransmitter section below). Kanner noted that over half his initial cases had feeding difficulties and excessive vomiting as infants (1943). Mercury, which binds to sulfur groups (Clarkson, 1992), is known to cause gastroenteritis (Kark et al, 1971). For example, a four year old with diarrhea was initially diagnosed with gastroenteritis (Florentine and Sanfilippo, 1991). A pre-adolescent with mercury vapor poisoning developed nausea, abdominal pain, poor appetite, rectal itching, and diarrhea; she frequently strained to have a bowel movement, and was at one point diagnosed with colitis (Fagala and Wigg, 1992). Incontinence of urine and stool are observed in infants and children exposed preand postnatally in Iraq (Amin-Zaki, 1974 and 1978). In another case, a 28 year old woman with occupational exposure to mercury vapor developed watery stools (Ross et al, 1977). Diarrhea and digestive disturbance were seen in a dentist with measurable mercury levels; there was obesity in another dentist (Smith, 1977). A 44 year old man poisoned with thimerosal given intramuscularly developed gastrointestinal bleeding, which looked like hemorrhaging colitis (Lowell et al, 1996). Intense exposure to mercury vapor can cause abdominal 22 Copyrighted document, SafeMinds ( In another rat experiment, Hg was found to increase the permeability of intestinal epithelial tissues (Watzl et al, 1999). Although renal function is commonly impaired from Hg exposure, such impairment would not be expected if the mercury exposure occurred from thimerosal injections, since kidney function may be unaffected when mercury is injected or inhaled (Davis et al, 1994; Fagala and Wigg, 1992). For example, although thimerosal ingested orally by a 44 year old man resulted in renal tubular failure and gingivitis (Pfab et al, 1996), renal function was normal in another 44 year old man injected intramuscularly with thimerosal (Lowell et al, 1996). Relatedly, mercury may cause low sulfate by its ability to irreversibly inhibit the sulfate transporter Na-Si cotransporter NaSi-1 present in kidneys and intestines, thus preventing sulfate absorption (Markovitch and Knight, 1998). Among the sulfhydryl groups, or thiols, mercury has special affinity for purines and pyrimidines, as well as other subcellular substances (Clarkson, 1992; Koos and Longo, 1976). Errors in purine or pyrimidine metabolism are known to result in classical autism or autistic features in some cases (Gillberg and Coleman, 1992, p. Likewise, yeast strains sensitive to Hg are those which have innately low levels of tyrosine synthesis. Glutathione: Glutathione is one of the primary means through which the cells detoxify heavy metals (Fuchs et al, 1997), and glutathione in the liver is a primary substrate by which body clearance of organic mercury takes place (Clarkson, 1992). Mercury, by preferentially binding with glutathione and/or preventing absorption of sulfate, reduces glutathione bioavailability. Edelson and Cantor (1998) have found a decreased ability of the liver in autistic subjects to detoxify heavy metals. Alternatively, low glutathione can be a manifestation of chronic infection (Aukrust et al, 1996, 1995; Jaffe et al, 1993), and infection-induced glutathione deficiency would be more likely in the presence of immune impairments derived from mercury (Shenkar et al, 1998). Glutathione peroxidase activities were reported to be abnormal in the erythrocytes of autistic children (Golse et al, 1978). Mitochondria: Disturbances of brain energy metabolism have prompted autism to be hypothesized as a mitochondrial disorder (Lombard, 1998). There is a frequent association of lactic acidosis and carnitine deficiency in autistic patients, which suggests excessive nitric oxide production in mitochondria (Lombard, 1998; Chugani et al, 1999), and again, mercury may be a participant. Immune System A variety of immune alterations are found in autism-spectrum children (Singh et al, 1993; Gupta et al, 1996; Warren et al, 1986 & 1996; Plioplys et al, 1994), and these appear to be etiologically significant in a variety of ways, ranging from autoimmunity to infections and vaccination responses. Glutathione and cysteine are essential components of lymphocyte activation, and their depletion may result in lymphocyte dysfunction. Allergy, asthma, and arthritis: Individuals with autism are more likely to have allergies and asthma, and autism occurs at a higher than expected rate in families with a history of autoimmune diseases such as rheumatoid arthritis and hypothyroidism (Comi and Zimmerman, 1999; Whitely et al, 1998). Relative to the general population, prevalence of selective IgA deficiency has been found in autism (Warren et al); individuals with selective IgA deficiency are more prone to allergies and autoimmunity (Gupta et al, 1996). Atypical responses to mercury have been ascribed to allergic or autoimmune reactions (Gosselin et al, 1984; Fournier et al, 1988), and a genetic predisposition for Hg reaction may explain why sensitivity to this metal varies so widely by individual (Rohyans et al, 1984; Nielsen & Hultman, 1999). Those with acrodynia are also more likely to suffer from asthma, to have poor immune system function (Farnesworth, 1997), and to experience intense joint pains suggestive of rheumatism (Clarkson, 1997). Rheumatoid arthritis with joint pain has been observed as a familial trait in autism (Zimmerman et al, 1993). A subset of autistic subjects had a higher rate of strep throat and elevated levels of B lymphocyte antigen D8/17, which has expanded expression in rheumatic fever and may be implicated in obsessive-compulsive behaviors (DelGiudiceAsch & Hollander, 1997). Iraqi mothers and children developed muscle and joint pain (Amin-Zaki, 1979), and acrodynia is marked by joint pain (Farnesworth, 1997). Sore throat is occasionally a presenting sign in mercury poisoning (Vroom and Greer, 1972). A 12 year old with mercury vapor poisoning, for example, had joint pains as well as a sore throat; she was positive on a streptozyme test, and a diagnosis of rheumatic fever was made; she improved on penicillin (Fagala and Wigg, 1992). Acrodynia, which is almost never seen in adults, was also observed in a 20 year old male with a history of sensitivity reactions and rheumatoid-like arthritis, who received ethylmercury via injection in gammaglobulin (Matheson et al, 1980). One effective chelating agent, penicillamine, is also effective for rheumatoid arthritis (Florentine and Sanfilippo, 1991). Mercury can induce an autoimmune response in mice and rats, and the response is both dose-dependent and genetically determined. The autoimmune response depends on the H-2 haplotype: if the strain of mice does not have the susceptibility haplotype, there is no autoimmune response; the most sensitive strains show elevated antibody titres at the lowest dose; and the less susceptible strain responds only at a medium dose (Nielsen & Hultman, 1999). Interestingly, Hu et al (1997) were able to induce a high proliferative response in lymphocytes from even low responder mouse strains by washing away excess mercury after pre-treatment, while chronic exposure to mercury induced a response only in high-responder strains. Autoimmunity and neuronal proteins: Based upon research and clinical findings, Singh has been suggesting for some time an autoimmune component in autism (Singh, Fudenberg et al, 1988). These findings were confirmed in rats and mice, and there were significant correlations between IgG titers and subclinical deficits in sensorimotor function. A high incidence of anti-cerebellar immunoreactivity which was both IgG and IgM in nature has been found in autism, and there is a higher frequency of circulating antibodies directed against neuronal antigens in autism as compared to controls (Plioplys, 1989; Connolly et al, 1999). Furthermore, Singh and colleagues have found that 50% to 60% of autistic subjects tested positive for the myelin basic protein antibodies (1993) and have hypothesized that autoimmune responses are related to an increase in select cytokines and to elevated serotonin levels in the blood (Singh, 1996; Singh, 1997). Since anti-cerebellar antibodies have been detected in autistic blood samples, ongoing damage may arise as these antibodies find and react with neural antigens, thus creating autoimmune processes possibly producing symptoms such as ataxia and tremor. Relatedly, the cellular damage to Purkinje and granule cells noted in autism (see below) may be mediated or exacerbated by antibodies formed in response to neuronal injury (Zimmerman et al, 1993). T-cells, monocytes, and natural killer cells: Many autistics have skewed immune-cell subsets and abnormal T-cell function, including decreased responses to T-cell mitogins (Warren et al, 1986; Gupta et al, 1996). One recent study reported increased neopterin levels in urine of autistic children, indicating activation of the cellular immune system (Messahel et al, 1998). Both high dose and chronic low-level mercury exposure kills lymphocytes, T-cells, and monocytes in humans. At low, chronic doses, the depressed immune function may appear asymptomatic, without overt signs of immunotoxicity. Methylmercury exposure would be especially harmful in individuals with already suppressed immune systems (Shenker et al, 1998). Mercury increases cytosolic free calcium levels [Ca2+]i in T lymphocytes, and can cause membrane damage at longer incubation times (Tan et al, 1993). Hg has also been found to cause chromosomal aberrations in human lymphocytes, even at concentrations below those causing overt poisoning (Shenkar et al, 1998; Joselow et al, 1972), and to inhibit rodent lymphocyte proliferation and function in vitro. Depending on genetic predisposition, mercury causes activation of the immune system, especially Th2 subsets, in susceptible mouse strains (Johansson et al, 1998; Bagenstose et al, 1999; Hu et al, 1999). Many autistic children have reduced natural killer cell function (Warren et al, 1987; Gupta et al, 1996), and many have a sulfation deficiency (Alberti, 1999). As noted previously, decreased levels of glutathione, observed in autistic and mercury poisoned populations, are associated with impaired immunity (Aukrust et al, 1995 and 1996; Fuchs and Schofer, 1997). Experimentally, primates have the highest levels in the brain relative to other organs (Clarkson, 1992). Methylmercury easily crosses the blood-brain barrier by binding with cysteine to form a molecule that is nearly identical to methionine. This molecule methylmercury cysteine is transported on the Large Neutral Amino Acid across the bbb (Clarkson, 1992). Inorganic mercury is unable to cross back out of the bbb (Pedersen et al, 1999) and is more likely than the organic form to induce an autoimmune response (Hultman and Hansson-Georgiadis, 1999). Furthermore, although most cells respond to mercurial injury by modulating levels of glutathione, metallothionein, hemoxygenase, and other 29 Copyrighted document, SafeMinds ( While damage has been observed in a number of brain areas in autism, many functions are spared (Dawson, 1996). In mercury exposure, damage is also selective (Ikeda et al, 1999; Clarkson, 1992), and the list of Hg-affected areas is remarkably similar to the neuroanatomy of autism. Cerebellum, Cerebral Cortex, & Brainstem: Autopsy studies of carefully selected autistic individuals revealed cellular changes in cerebellar Purkinje and granule cells (Bauman and Kemper, 1988; Ritvo et al, 1986). Mercury can induce cellular degeneration within the cerebral cortex and leads to similar processes within granule and Purkinje cells of the cerebellum (Koos and Longo, 1976; Faro et al, 1998; Clarkson, 1992; see also Anuradha, 1998; Magos et al, 1985). Furthermore, cerebellar damage is implicated in alterations of coordination, balance, tremors, and sensations (Davis et al, 1994; Tokuomi et al, 1982), and these findings are consistent with Hg-induced disruption in cerebellar synaptic transmission between parallel fibers or climbing fibers and Purkinje cells (Yuan & Atchison, 1999). In monkeys, mercury preferentially accumulated in the deepest pyramidal cells and fiber systems. These substances tend to inhibit lipid peroxidation and thereby suppress mercury toxicity (Fukino et al, 1984). Importantly, granule and Purkinje cells have increased risk for mercury toxicity because they produce low levels of these protective substances (Ikeda et al, 1999; Li et al, 1996). The peripheral polyneuropathy examined in Iraqi victims was believed to have resulted from brain stem damage (Von Burg and Rustam, 1974). Pathology affecting the temporal lobe, particularly the amygdala, hippocampus, and connected areas, is seen in autistic patients and is characterized by increased cell density and reduced neuronal size (Abell et al, 1999; Hoon and Riess, 1992; Otsuka, 1999; Kates et al, 1998; Bauman and Kemper, 1985). The basal ganglia also show lesions in some cases (Sears, 1999), including decreased blood flow (Ryu et al, 1999). Mercury can accumulate in the hippocampus and amygdala, as well as the striatum and spinal chord (Faro et al, 1998; Lorscheider et al, 1995; Larkfors et al, 1991). One study has shown that areas of hippocampal damage from Hg were those which were unable to synthesize glutathione (Li et al, 1996). A 1994 study in primates found that mercury accumulates in the hippocampus and amygdala, particularly the pyramidal cells, of adults and offspring exposed prenatally (Warfvinge et al, 1994). The documenting of temporal lobe mercury provides a direct link between autism and mercury because, as cited previously, (i) mercury alters neuronal function, and (ii) the temporal lobe, and the amygdala in particular, are strongly implicated in autism. Bachevalier (1996) has shown that infant monkeys with early damage to the amygdaloid complex exhibit many autistic behaviors, including social avoidance, blank expression, lack of eye contact and play posturing, and motor stereotypies. Hippocampal lesions, when combined with amygdaloid damage, increases the severity of symptoms. Also noteworthy is the fact that amygdala findings in autism and mercury literatures are paralleled in fragile X syndrome, a genetic disorder wherein many affected individuals have traits worthy of an autism diagnosis.
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