Umer Najib

Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

Fragile X Syndrome (FXS) is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of fragile X mental retardation protein affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation paradigms have recently been developed to non-invasively investigate cortical excitability using paired pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS) in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity). The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD), and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of non-invasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS-EEG

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor‐evoked potentials (MEPs) reflective of modulation of cortico‐spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta‐burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS‐induced EEG evoked potentials (TEPs), (iii) TMS‐induced EEG synchronization and (iv) eyes‐closed resting EEG. Our results show the expected cTBS‐induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes‐closed resting EEG, whereas it decreased single‐pulse TMS‐induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes‐closed resting EEG, whereas it increased single‐pulse TMS‐induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low‐frequency (theta and/or alpha) oscillators and desynchronizes high‐frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS‐induced plasticity outside of the motor cortex.

Transcranial Brain Stimulation: Clinical Applications and Future Directions

Noninvasive brain stimulation is a valuable investigative tool and has potential therapeutic applications in cognitive neuroscience, neurophysiology, psychiatry, and neurology. Transcranial magnetic stimulation (TMS) is particularly useful to establish and map causal brain-behavior relations in motor and nonmotor cortical areas. Neuronavigated TMS is able to provide precise information related to the individuals functional anatomy that can be visualized and used during surgical interventions and critically aid in presurgical planning, reducing the need for riskier and more cumbersome intraoperative or invasive mapping procedures. This article reviews methodological aspects, clinical applications, and future directions of TMS-based mapping.

A retrospective review of clinical presentation, thyroid autoimmunity, laboratory characteristics, and therapies used in patients with chronic idiopathic urticaria.

BACKGROUND Our knowledge of autoimmune characteristics of chronic idiopathic urticaria (CIU) is limited. OBJECTIVE To study the demographic, laboratory, and clinical patterns of a cohort of patients with CIU. METHODS We evaluated 236 patients with CIU seen in a recent 2-year span. For serum basophil activation testing (BAT-CD203), the samples were sent to the National Jewish Medical and Research Center for donor basophil CD203 expression assay (5% cell surface expression was considered a positive result). RESULTS Of the 236 patients with CIU, 77% were females with a mean age of 39 years. The mean age of males was 43 years. Of patients tested for BAT-CD203 (50 females and 8 males), 38% of females (n = 19) and 13% of males (n = 1) had positive test results. Of the 146 females and 42 males tested for thyroid autoimmunity (TA), 34% of females (n = 50) and 17% of males (n = 7) had underlying TA. Nine BAT-CD203-positive females (47%) had TA compared with 11 of 30 BAT-CD203-negative females (37%). No correlation was found between antinuclear antibodies and BAT-CD203. Cyclosporine or corticosteroids were used in 28% of the study population, with another 16% requiring a trial of additional third-line agents with or without prednisone/cyclosporine. There was no significant difference in the maximum number of medications used in subgroups based on the presence or absence of BAT-CD203 and TA. CONCLUSIONS The frequency of TA in patients with CIU was 30%, which is higher than that previously reported. The frequency of TA and BAT-CD203 positivity was higher in females. In this clinical cohort, there was no correlation between BAT-CD203 and TA.

Detailed analysis of allergic cutaneous reactions to spinal cord stimulator devices

The use of spinal cord stimulation (SCS) devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1–3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. “In vivo” testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and is helpful to differentiate an inflammatory reaction from infection. The role of skin patch testing for 96 hours may not be suited to detect inflammatory giant cell reactions that manifest several weeks post implantation.

An Update on Acute and Chronic Urticaria for the Primary Care Provider

Abstract Urticaria is a common dermatologic condition seen by primary care physicians. Urticaria can result in significant morbidity and a dramatic decline in quality of life. Acute urticaria is mostly an allergic or IgE-mediated reaction and tends to be self-limited, while chronic urticaria generally does not exhibit any specific external cause and is therefore considered idiopathic. Evidence suggests that up to 30% to 50% of idiopathic cases may be autoimmune and/or related to mast cell/basophil abnormalities. There is further evidence of an autoantibody to the high-affinity receptor for IgE (FcϵRI), specifically binding to the α-chain (FcϵRIα), which may be pathogenic. The treatment regimen for urticaria needs to be individualized as the severity and clinical pattern can vary considerably between patients. Histamine antagonists are the mainstays of therapy. For more severe or persistent cases, there are few Food and Drug Administration (FDA)-approved options, and there are limited data from controlled trials. Further research is required to develop safe and more effective agents for this disease.

Enhanced motor function and its neurophysiological correlates after navigated low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in stroke

BACKGROUND The net effect of altered interhemispheric interactions between homologous motor cortical areas after unilateral stroke has been previously reported to contribute to residual hemiparesis. Using this framework, we hypothesized that navigated 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional hemisphere would induce a stronger physiological and behavioural response in patients with residual motor deficit than in healthy subjects, because an imbalance in interhemispheric excitability may underlie motor dysfunction. METHODS Navigated rTMS was conducted in 8 chronic stroke patients (67.50±13.77 years) and in 8 comparable normal subjects (57.38±9.61 years). We evaluated motor function (Finger tapping, Nine Hole Peg test, Strength Index and Reaction Time) as well as the excitatory and inhibitory function (resting motor threshold, motor evoked potential amplitude, intra-cortical inhibition and facilitation, and silent period) of the stimulated and non-stimulated motor cortex before and after navigated rTMS. RESULTS rTMS induced an increase in excitability in the ipsilesional (non-stimulated) motor cortex and led to improved performance in the finger tapping task and pinch force task. These physiological and behavioral effects were more prominent (or robust) in the group of stroke patients than in the control group. CONCLUSION Navigated low-frequency rTMS involving precise and consistent targeting of the contralesional hemisphere in stroke patients enhanced the cortical excitability of the ipsilesional hemisphere and the motor response of the hemiparetic hand.

Anterior Disconnection Syndrome Revisited using Modern Technologies

An anterior disconnection syndrome was first described over 100 years ago by Liepmann and Maas1 and brought back to clinical awareness 50 years ago by Geschwind and Kaplan.2 Damage to the corpus callosum has been confirmed by postmortem analysis but precise anatomic along with its functional characterization has not been accomplished. We report a patient with the anterior disconnection syndrome after stroke. Diffusion tensor imaging (DTI) tractography and transcallosal neurophysiologic recordings confirmed the exact transcallosal disconnection.