Underlying Brain Abnormalities Research Articles

Epilepsy and Depression: How Are They Related?

When 2 medical conditions occur together more often than predicted by chance, they are called comorbid conditions. The observation that depression is connected to epilepsy (i.e., that they are comorbidities) raises many questions. How are the illnesses connected? Are both caused by a common underlying brain abnormality? Is there an abnormality of neurotransmitters responsible for both? Finally, does the same connection occur with other chronic medical illnesses? The authors of this study used asthma, another chronic medical illness, as a comparison. They looked at the rate of depression in people with asthma and compared this with that in people with epilepsy. Using the registry data, they were also able to look at the opposite possibility: that is, do people with depression have epilepsy more often?

Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain

Down syndrome (DS) is the most common genetic cause of intellectual disability and increases the risk of other brain-related dysfunctions, like seizures, early-onset Alzheimer's disease, and autism. To reveal the molecular profiles of DS-associated brain phenotypes, we performed a meta-data analysis of the developmental DS brain transcriptome at cell type and co-expression module levels. In the DS brain, astrocyte-, microglia-, and endothelial cell-associated genes show upregulated patterns, whereas neuron- and oligodendrocyte-associated genes show downregulated patterns. Weighted gene co-expression network analysis identified cell type-enriched co-expressed gene modules. We present eight representative cell-type modules for neurons, astrocytes, oligodendrocytes, and microglia. We classified the neuron modules into glutamatergic and GABAergic neurons and associated them with detailed subtypes. Cell type modules were interpreted by analyzing spatiotemporal expression patterns, functional annotations, and co-expression networks of the modules. This study provides insight into the mechanisms underlying brain abnormalities in DS and related disorders.

Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

CORRELATION BETWEEN BRAIN MAGNETIC RESONANCE CHANGES AND RESPONSE TO FUNCTIONALLY BASED REHABILITATION PROGRAM IN CHILDREN WITH SPASTIC CEREBRAL PALSY

Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood with prevalence rates of 2–3 per 1000 live births in developed countries. CP is the leading cause of physical disability in children. Thus, neuroimaging is currently recommended as a standard evaluation in children with cerebral palsy. Objective: To investigate the relationship and inter-relation between functional profiles including; gross motor function and manual ability, with brain magnetic resonance imaging characteristics in children with CP before and at end of functionally based exercise program. Patients and Methods: This study was carried out on twenty five spastic CP children of both genders at age ranged from 3 months old to 12 years old, attending the out-patient pediatric clinic of Bab Al Sha’reya University Hospital, during the period from May 2019 to December 2019. Results: Diplegia was the most common represented type, followed by quadriplegia and hemiplegia. The common causes were hypoxic ischemic encephalopathy (52%), Post-kernicterus CP (32%), and Post traumatic CP (16%). History of mother drug intake, hypoxia, pre-mature birth, cyanosis and severe RDS, delivery with caesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP. Conclusion: History of mother drug intake, hypoxia, pre-mature birth, cyanosis and severe RDS, delivery with cesarian section, neonatal convulsion, jaundice and post-kernicterus complication, and head trauma were significantly associated with increased risk of CP. MRI scan was useful in revealing underlying brain abnormalities and speculating on the etiology of cerebral palsy.

Research on a 'drug-centred' approach to psychiatric drug treatment: assessing the impact of mental and behavioural alterations produced by psychiatric drugs.

This article explores an alternative understanding of how psychiatric drugs work that is referred to as the drug-centred model of drug action. Unlike the current disease-centred model, which suggests that psychiatric drugs work by correcting an underlying brain abnormality, the drug-centred model emphasises how psychiatric drugs affect mental states and behaviour by modifying normal brain processes. The alterations produced may impact on the emotional and behavioural problems that constitute the symptoms of mental disorders. Arguments are put forward that justify the consideration of the drug-centred model. The research necessary to support the prescription of drugs according to such a model is explored. Evidence from neurochemistry and comparative drug trials do not confirm the disease-centred model of drug action. Since psychiatric drugs are recognised to have mind- and behaviour-altering properties, the drug-centred model constitutes a plausible alternative. The drug-centred model suggests that research is needed to identify all the alterations produced by various sorts of drugs, both acute and long term, and how these might interact with the symptoms and problems associated with different mental disorders. This requires detailed animal and volunteer studies and data from patients prescribed drug treatment long term, along with placebo-controlled and comparative trials that look at the overall impact of drug-induced alterations on well-being and functioning as well as symptoms. Research is also needed on alternative ways of fulfilling the function of drug treatment. The moral aspect of using drugs to modify behaviour rather than treat disease needs honest and transparent consideration. It is hoped this discussion will encourage the psychiatric and pharmaceutical research community to provide more of the information that is required to use psychiatric drugs safely and effectively.

Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review.

β-lactam antibiotics are commonly prescribed antibiotic drugs. To describe the clinical characteristics, risk markers and outcomes of β-lactam antibiotic-induced neurological adverse effects, we performed a general literature review to provide updated clinical data about the most used β-lactam antibiotics. For selected drugs in each class available in France (ticarcillin, piperacillin, temocillin, ceftazidime, cefepime, cefpirome, ceftaroline, ceftobiprole, ceftolozane, ertapenem and aztreonam), a systematic literature review was performed up to April 2016 via an electronic search on PubMed. Articles that reported original data, written in French, Spanish, Portuguese or English, with available individual data for patients with neurological symptoms (such as seizure, disturbed vigilance, confusional state, myoclonia, localising signs, and/or hallucinations) after the introduction of a β-lactam antibiotic were included. The neurological adverse effects of piperacillin and ertapenem are often described as seizures and hallucinations (>50 and 25% of cases, respectively). Antibiotic treatment is often adapted to renal function (>70%), and underlying brain abnormalities are seen in one in four to one in three cases. By contrast, the neurological adverse drug reactions of ceftazidime and cefepime often include abnormal movements but few hallucinations and seizures. These reactions are associated with renal insufficiency (>80%) and doses are rarely adapted to renal function. Otherwise, it appears that monobactams do not have serious neurological adverse drug reactions and that valproic acid and carbapenem combinations should be avoided. The onset of disturbed vigilance, myoclonus, and/or seizure in a patient taking β-lactam antibiotics, especially if associated with renal insufficiency or underlying brain abnormalities, should lead physicians to suspect adverse drug reactions and to consider changes in antibacterial therapy.

Sleep-related hypermotor epilepsy: Long-term outcome in a large cohort.

Objective:To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).Methods:We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.Results:We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR.Conclusions:Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

Epidemiology of neonatal seizures

Neonatal seizures are common and frequently indicate significant underlying brain abnormality. The epidemiology of neonatal seizures has been evaluated in several population and hospital-based studies and these investigations have lead to identification of important maternal, intrapartum and infant risk factors. Identifying and avoiding risks factors for neonatal seizures may lead to lower infant neurological morbidity and mortality.

Developmental disruptions underlying brain abnormalities in ciliopathies.

Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies.

Voxel-Based Meta-Analytical Evidence of Structural Disconnectivity in Major Depression and Bipolar Disorder

BackgroundIdentification of white matter microstructure differences and similarities between major depression and bipolar disorder is a necessary step to better understand the underlying brain abnormalities in affective disorders and target more effective treatments. However, research has not yet yielded robust conclusions. We report here a meta-analysis of diffusion tensor imaging studies in these conditions. MethodsA comprehensive literature search was conducted up to 2014 to identify studies comparing fractional anisotropy (FA) between patients and control subjects. Results were combined to identify white matter abnormalities in major depression (736 patients vs. 668 control subjects) and bipolar disorder (536 patients vs. 489 control subjects). Effect size comparison and conjunction analysis allowed identification of similarities and differences between the disorders. ResultsA significant decrease in FA in the genu of the corpus callosum characterized both conditions. The comparison between unipolar and bipolar disorders revealed a greater decrease in FA in the left posterior cingulum in bipolar disorder. Studies that adopted tract-based spatial statistics methodology showed more pronounced reductions in these regions compared with voxel-based analyses. ConclusionsMajor depression and bipolar disorder are characterized by abnormalities in white matter tracts of the genu of the corpus callosum that connect the two hemispheres of the prefrontal cortex implicated in mood regulation. Bipolar disorder was associated with reduced white matter integrity in the left posterior cingulum, which may contribute to cognitive impairment described in this condition. Tract-based spatial statistics may be a more sensitive technique to detect white matter abnormalities in these regions compared with voxel-based analyses.

Developmental disruptions underlying brain abnormalities in ciliopathies

Developmental disruptions underlying brain abnormalities in ciliopathies

PROTON MR SPECTROSCOPY IN THE DIAGNOSTIC EVALUATION OF SUSPECTED MITOCHONDRIAL DISEASE IN IRAN

Mitochondrial diseases are a group of inherited disorders Caused by a derangement of mitochondrial respiration. The clinical manifestations are heterogeneous, and the diagnosis is often based on information acquired from multiple levels of inquiry that require a variety of diagnostic tests for proper determination. Neuroimaging may play a significant role in diagnosis. The various modalities of nuclear magnetic resonance imaging (MRI) allow for multiple independent detection procedures that can give important anatomical and metabolic clues for diagnosis when the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. The non-invasive nature of neuroimaging also allows for longitudinal studies. To date, no pathognomonic correlation between specific genetic defect and neuroimaging findings have been described. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. Magnetic resonance imaging changes may be nonspecific; however, certain neuroimaging results can give important clues that a patient may have a mitochondrial disease. Conventional MRI may show Brain atrophy, supratentorial white matter lesions, basal ganglia involvement deep gray structural abnormalities, and delayed myelination are the most frequent anomalies in the definite cases. Also they may represent clearly characteristic of a given disorder such as strokelike lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyper intensities with or without associated gray matter involvement may also be observed or stroke-like lesions that do not respect vascular territories. Chemical techniques such as proton magnetic resonance spectroscopy (MRS) may demonstrate high levels of lactate or succinate. When found, these results are suggestive of a mitochondrial disease. MRI and MRS studies may also show nonspecific findings such as delayed myelination or non-specific leukodystrophies picture. However, in the context of other biochemical, structural, and clinical findings, even non-specific findings may support further diagnostic testing for potential mitochondrial disease. Once a diagnosis has been established, these non-invasive tools can also aid in following disease progression and evaluate the effects of therapeutic interventions.

Focal Scn1a knockdown induces cognitive impairment without seizures

Cognitive impairment is a common comorbidity in pediatric epilepsy that can severely affect quality of life. In many cases, antiepileptic treatments fail to improve cognition. Therefore, a fundamental question is whether underlying brain abnormalities may contribute to cognitive impairment through mechanisms independent of seizures. Here, we examined the possible effects on cognition of Nav1.1 down-regulation, a sodium channel principally involved in Dravet syndrome but also implicated in other cognitive disorders, including autism and Alzheimer's disease. Using an siRNA approach to knockdown Nav1.1 selectively in the basal forebrain region, we were able to target a learning and memory network while avoiding the generation of spontaneous seizures. We show that reduction of Nav1.1 expression in the medial septum and diagonal band of Broca leads to a dysregulation of hippocampal oscillations in association with a spatial memory deficit. We propose that the underlying etiology responsible for Dravet syndrome may directly contribute to cognitive impairment in a manner that is independent from seizures.

Value of preoperative imaging in the diagnostics of isolated metopic suture synostosis: A risk–benefit analysis

Radiographic evaluation including plain radiographies and computed tomographic (CT) scans are considered as a necessary tool for diagnosis of craniosynostosis. As recently concerns about harmful effects of ionising radiation in children have been raised, some authors have suggested the use of magnetic resonance imaging (MRI) as a helpful alternative in preoperative imaging of patients with isolated metopic synostosis. Besides confirming the diagnosis of trigonocephaly, MRI is the superior technique for the evaluation of underlying brain anomalies. However, if the benefit of preoperative imaging justifies possible side effects is still discussed controversially. Hence, this study investigated the value of preoperative imaging for the diagnosis of isolated synostosis of the metopic suture compared to a sole clinical examination. In a series of 63 cases with isolated metopic craniosynostosis operated at the Department of Oral and Maxillofacial Surgery, 48 (76.2%) patients received additional radiography or MRI investigation, while in 15 (23.8%) patients the diagnosis was based on clinical examinations only. In all patients, diagnosis was confirmed intra-operatively by a fused metopic suture. CT scans with three-dimensional reconstruction (12.5%) or plain radiographs (39.6%) did not provide any additional benefit for the diagnosis or the surgical treatment. In 23 patients (47.9%), MRI showed the typical soft-tissue alterations like triangular brain deformation in the frontal area. Besides these findings, no brain or other underlying anomalies were diagnosed which had required any additional treatment. The incidence of underlying brain abnormalities in isolated metopic synostosis seemed not to be different from that of the general population. As the characteristic clinical manifestations were sufficient for an accurate diagnosis of isolated metopic synostosis, and with respect to the biological effects of ionising radiation and risks of sedation especially in infants, preoperative imaging should be reduced to a minimum.

Goal‐directed arm movements in children with fetal alcohol syndrome: a kinematic approach

Although many studies have documented deficits in general motor functioning in children with fetal alcohol syndrome (FAS), few have employed detailed measurements to explore the specific nature of such disabilities. This pilot study explores whether three-dimensional (3D) kinematic analysis may generate increased knowledge of the effect of intrauterine alcohol exposure on motor control processes by detecting atypical upper-limb movement pattern specificity in children with FAS relative to typically developing (TD) children. Left and right arm and head movements during a sequential unimanual goal-directed precision task in a sample of children with FAS and in TD children were registered by an optoelectronic tracking system (ProReflex, Qualisys Inc.). Children with FAS demonstrated evidently poorer task performance compared with TD children. Additionally, analyses of arm movement kinematics revealed atypical spatio-temporal organization in the children with FAS. In general, they exhibited longer arm movement trajectories at both the proximal and distal level, faster velocities at the proximal level but slower at the distal level, and more segmented distal movements. Children with FAS also showed atypically augmented and fast head movements during the task performance. Findings indicate neuromotor deficits and developmental delay in goal-directed arm movements because of prenatal alcohol exposure. It is suggested that 3D kinematic analysis is a valid technique for furthering the understanding of motor control processes in children with FAS/fetal alcohol spectrum disorders. A combination with relevant neuroimaging techniques in future studies would enable a more clear-cut interpretation of how atypical movement patterns relate to underlying brain abnormalities.

The use of neuroimaging in the diagnosis of mitochondrial disease

Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease.

Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: From tuberous sclerosis to common acquired epilepsies

Most current treatments for epilepsy are symptomatic therapies that suppress seizures but do not affect the underlying course or prognosis of epilepsy. The need for disease-modifying or "antiepileptogenic" treatments for epilepsy is widely recognized, but no such preventive therapies have yet been established for clinical use. A rational strategy for preventing epilepsy is to target primary signaling pathways that initially trigger the numerous downstream mechanisms mediating epileptogenesis. The mammalian target of rapamycin (mTOR) pathway represents a logical candidate, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. The importance of the mTOR pathway in epileptogenesis is best illustrated by tuberous sclerosis complex (TSC), one of the most common genetic causes of epilepsy. In mouse models of TSC, mTOR inhibitors prevent the development of epilepsy and underlying brain abnormalities associated with epileptogenesis. Accumulating evidence suggests that mTOR also participates in epileptogenesis due to a variety of other causes, including focal cortical dysplasia and acquired brain injuries, such as in animal models following status epilepticus or traumatic brain injury. Therefore, mTOR inhibition may represent a potential antiepileptogenic therapy for diverse types of epilepsy, including both genetic and acquired epilepsies.

Establishing the Diagnosis of Cerebral Palsy

Cerebral palsy (CP) is a diagnosis of considerable concern to obstetricians, but the diagnosis of CP can be challenging, and may need to be confirmed by an experienced practitioner, ideally a child neurologist or psychiatrist. It is important not to make the diagnosis too early in infancy, especially when the signs are not severe, as resolution of early neuromotor abnormalities does occur, particularly in premature infants. Exclusion of genetic/metabolic disorders presenting with CP-like findings is important. The degree of activity limitation should be characterized; labeling children as having CP on the basis of abnormal examination findings alone without evidence of activity limitation is not useful. Brain imaging can be helpful in pinpointing the location of the underlying brain abnormality and sometimes provides etiologically useful information.

Diagnosis and Management of Unilateral Third-Trimester Hydrocephalus: A Multidisciplinary Approach

Hydrocephalus is a pathological increase in cerebrospinal fluid. This condition may occur when production exceeds absorption. Prior reports describe prenatally diagnosed unilateral hydrocephalus with varying outcomes depending on underlying brain abnormalities, karyotypic abnormalities, and infection. Prenatal ultrasound is a valuable diagnostic tool in the identification of hydrocephalus. Obstacles such as near-field artifact, additional intracranial abnormalities, fetal positioning, and maternal habitus often make the diagnosis difficult. Antenatal diagnosis is important for emotional preparation and for transfer to a tertiary center where appropriate facilities and subspecialists are available. We present a case of right-sided hydrocephalus and mild left-sided ventriculomegaly diagnosed in the third trimester. Fetal brain magnetic resonance imaging confirmed the sonographic diagnosis, which allowed the multidisciplinary fetal team to meet with the patient and formulate a management plan prior to delivery.

Rapid morphological brain abnormalities during acute methamphetamine intoxication in the rat: An experimental study using light and electron microscopy

This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood–brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (i.v.) catheter were exposed to METH (9 mg/kg) at standard (23 °C) and warm (29 °C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological (38–42 °C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5 °C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na +, K +, Cl −) contents, immunostained for albumin and glial fibrillary acidic protein (GFAP), and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29 °C than 23 °C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse.