Peer-Reviewed Journal Articles
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- ItemCentral Nervous System Acting Drugs in Treatment of Migraine Headache(2012) Samsam, MohtashemMigraine is a primary headache disorder with an unknown pathophysiology. The growing evidence in recent years indicates migraine being a brain disorder, a sensory dysmodulation, and a system failure of normal sensory processing of the brainstem that involves the vascular tone and pain. At the moment, triptan family and NSAIDs are the first choice drugs for the treatment of acute migraine. There are several prophylactic drugs including the antiepileptic drugs (AEDs), betablockers, and Ca2+ channel blockers that are used for the treatment of migraine. Although many drugs including the triptans, NSAIDs, and others target the peripheral sites of activation, several novel drugs are being developed to target neural sites of action in the central nervous system (CNS). The first trigeminal synapses in the brain stem as well as the ascending and descending pathways and higher brain centers are involved in the transmission of pain and therefore be the main targets of several drugs some of which are in clinical trials. Central sensitization may also aggravate the headache and some drugs tend to alleviate pain by targeting neurotransmitters, receptors, or signalling molecules involved in this phenomenon. This article discusses the CNS acting novel drugs and those that are currently in use for the treatment of migraine.
- ItemConcordance and Discordance Between Measured Balance and Perceived Balance and the Effect on Gait Speed and Falls Following Stroke(2016) Liphart, Jodi; Gallichio, Joann; Tilson, Julie K.; Pei, Qinglin; Wu, Samuel S.; Duncan, Pamela W.Objective: To ascertain the existence of discordance between perceived and measured balance in persons with stroke and to examine the impact on walking speed and falls. Design: A secondary analysis of a phase three, multicentered randomized controlled trial examining walking recovery following stroke. Subjects: A total of 352 participants from the Locomotor Experience Applied Post-Stroke (LEAPS) trial. Methods: Participants were categorized into four groups: two concordant and two discordant groups in relation to measured and perceived balance. Number and percentage of individuals with concordance and discordance were evaluated at two and 12 months. Walking speed and fall incidence between groups were examined. Main measures: Perceived balance was measured by the Activities-Specific Balance Confidence scale, measured balance was determined by the Berg Balance Scale and gait speed was measured by the 10-meter walk test. Results: Discordance was present for 35.8% of participants at two months post stroke with no statistically significant change in proportion at 12 months. Discordant participants with high perceived balance and low measured balance walked 0.09 m/s faster at two months than participants with concordant low perceived and measured balance (p < 0.05). Discordant participants with low perceived balance and high measured balance walked 0.15 m/s slower than those that were concordant with high perceived and measured balance (p ⩽ 0.0001) at 12 months. Concordant participants with high perceived and measured balance walked fastest and had fewer falls. Conclusions: Discordance existed between perceived and measured balance in one-third of individuals at two and 12 months post-stroke. Perceived balance impacted gait speed but not fall incidence.
- ItemDifferential Diagnosis of Deep Gluteal Pain in a Female Runner with Pelvic Involvement: A Case Report(2013) Podschun, Laura; Hanney, William J.; Kolber, Morey J.; Garcia, Ashley; Rothschild, Carey E.Background: Gluteal injuries, proximal hamstring injuries, and pelvic floor disorders have been reported in the literature among runners. Some suggest that hip, pelvis, and/or groin injuries occur in 3.3% to 11.5% of long distance runners. The purpose of this case report is to describe the differential diagnosis and treatment approach for a patient presenting with combined hip and pelvic pain. Case description: A 45-year-old female distance runner was referred to physical therapy for proximal hamstring pain that had been present for several months. This pain limited her ability to tolerate sitting and caused her to cease running. Examination of the patient’s lumbar spine, pelvis, and lower extremity led to the initial differential diagnosis of hamstring syndrome and ischiogluteal bursitis. The patient’s primary symptoms improved during the initial four visits, which focused on education, pain management, trunk stabilization and gluteus maximus strengthening, however pelvic pain persisted. Further examination led to a secondary diagnosis of pelvic floor hypertonic disorder. Interventions to address the pelvic floor led to resolution of symptoms and return to running. Outcomes: Pain level on the Visual Analog Scale decreased from 7/10 to 1/10 over the course of treatment. The patient was able to return to full sport activity and improved sitting tolerance to greater then two hours without significant discomfort. Discussion: This case suggests the interdependence of lumbopelvic and lower extremity kinematics in complaints of hamstring, posterior thigh and pelvic floor disorders. This case highlights the importance of a thorough examination as well as the need to consider a regional interdependence of the pelvic floor and lower quarter when treating individuals with proximal hamstring pain.
- ItemExosomes Derived from Cardiac Parasympathetic Ganglionic Neurons Inhibit Apoptosis in Hyperglycemic Cardiomyoblasts(2019) Singla, Reetish; Garner, Kaley H.; Samsam, Mohtashem; Cheng, Zixi; Singla, Dinender K.Diabetic cardiomyopathy is known to involve two forms of cardiac cell death: apoptosis and necrosis. However, it remains unknown whether hyperglycemia-induced apoptosis in the H9c2 cell culture system is inhibited by parasympathetic ganglionic neurons (PGN) derived exosomes (exos). We isolated PGN and sympathetic ganglionic neurons (SGN) from the right stellate ganglion in rats, and derived exos from these sources. H9c2 cells were divided into 4 groups: (1) Control, (2) H9c2 + Glucose (100 mmol/L), (3) H9c2 + Glucose + PGN-exos, and (4) H9c2 + Glucose + SGN-exos. We determined cell proliferation and viability with an MTT assay kit, and assessed apoptotic cell death with TUNEL staining and ELISA. Data were further confirmed by analyzing the presence of pro-apoptotic proteins Caspase-3 and Bax, and anti-apoptotic protein Bcl-2. Glucose exposed H9c2 cells significantly reduced cell viability, which was improved by PGN-exos, but not by SGN-exos. Furthermore, increased apoptosis in hyperglycemia in H9c2 cells was confirmed with TUNEL staining and cell death ELISA which demonstrated significantly (p < 0.05) reduction with PGN-exos treatment, but not with SGN-exos. Moreover, high expression of pro-apoptotic proteins Caspase-3 and Bax was reduced following treatment with PGN-exos; however, SGN-exos were unable to reduce the expression. Significantly reduced anti-apoptotic protein Bcl-2 following glucose treatment was improved with PGN-exos. Therefore, our data suggest that hyperglycemia induces apoptosis in H9c2 cells and decreases cell viability, and that PGN-exos are able to inhibit apoptosis, improve cell viability, and restore levels of anti-apoptotic protein Bcl-2.
- ItemNeuromodulation in the Treatment of Migraine: Progress in Nerve Stimulation(2017) Samsam, Mohtashem; Ahangari, RahelehMigraine is a type of primary headache disorder that can become chronic and disabling. The exact pathomechanism of migraine is not known very well and its treatment is also difficult in some cases. There are several medications for the acute and preventive treatment of migraine including the “triptan” family drugs, nonsteroidal anti-inflammatory drugs, anti-epileptic drugs, beta-blockers, and Ca2+-channel blockers1 and those against calcitonin gene-related peptide or its receptor that are reviewed elsewhere.2 However, there are some medically intractable headaches or patient management is unsatisfactory or medications are poorly tolerated3 or there are contraindications. Therefore, neuromodulation and nerve stimulation methods that have proven effective in clinical research may provide an additional treatment option for acute and preventive treatment of migraine. In this brief review, we will discuss recent advances using neuromodulatory techniques that are currently used in the treatment of headaches in clinical studies. These include the electrical stimulation of occipital nerve, sphenopalatine ganglion, supraorbital nerve, and transcutaneous electrical stimulation of vagus nerve as well as single-pulse transcranial magnetic stimulation. Several clinical studies have conducted neurostimulation for the acute and preventive treatment of migraine in recent years but more studies are necessary to see their efficacy and long-term effect.
- ItemNeuropeptides and Other Chemical Mediators, and the Role of Anti-inflammatory Drugs in Primary Headaches(2010) Samsam, Mohtashem; Covenas, Rafael; Ahangari, Raheleh; Yajeya, JavierPrimary headaches including the migraine, cluster, and tension headaches are common neurological disorders which cause pain and disability to the patients. The pathomechanism of migraine is not very well understood however, current clinical findings indicate a possible primary brain disorder due to activation of the brain and brainstem as triggers for migraine. The headache phase of migraine may be due to activation of the peripheral nerves including the trigeminal nerve and others innervating the cranial blood vessels and release of vasoactive substances including the calcitonin generelated peptides (CGRP), possibly leading to vasodilation and brainstem activation. Several of our studies in an experimental model of pain using electrical stimulation of the trigeminal ganglion in rats focused on various neuropeptides release from the peripheral and central trigeminal nerve terminals, however, clinically only the CGRP in migraine and CGRP and vasoactive intestinal peptide (VIP) in cluster headache were found in patient's blood. Although several drugs are used in the treatment of migraine, the non-steroid anti-inflammatory drugs (NSAIDs) and the triptan family of drugs are the first choice drugs recommended for the treatment of acute migraine headache. Although clinically very few studies detected other vasoactive/inflammatory molecules in the blood of migraine patients, sensitization of peripheral axons can involve many inflammatory mediators affecting the peripheral tissue substrates of pain. Moreover, central sensitization in the trigeminal nucleus can also contribute to additional pain responses. This article reviews neuropeptides and other molecules involved in primary headaches and major drugs proposed for their treatment in recent years.
- ItemPathophysiology of Autism Spectrum Disorders: Revisiting Gastrointestinal Involvement and Immune Imbalance(2014) Samsam, Mohtashem; Ahangari, Raheleh; Naser, Saleh A.Autism spectrum disorders (ASD) comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors. Several genes have been implicated in the pathogenesis of ASD, most of them are involved in neuronal synaptogenesis. A number of environmental factors and associated conditions such as gastrointestinal (GI) abnormalities and immune imbalance have been linked to the pathophysiology of ASD. According to the March 2012 report released by United States Centers for Disease Control and Prevention, the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms. Although there is a strong genetic base for the disease, several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem. Many children suffering from ASD have GI problems such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, and intestinal infections. A number of studies focusing on the intestinal mucosa, its permeability, abnormal gut development, leaky gut, and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas. GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children. Maternal infection or autoimmune diseases have been suspected. Activation of the immune system during early development may have deleterious effect on various organs including the nervous system. In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
- ItemRehabilitation of a Female Dancer with Patellofemoral Pain Syndrome: Applying the Concepts of Regional Interdependence in Practice(2010) Welsh, Caitlyn; Hanney, William J.; Podschun, Laura; Kolber, Morey J.Due to complex movements and high physical demands, dance is often associated with a multitude of impairments including pain of the low back, pelvis, leg, knee, and foot. This case report provides an exercise progression, emphasizing enhancement of strength and neuromuscular performance using the concept of regional interdependence in a 17 year old female dancer with patellofemoral pain syndrome.
- ItemThe Use of Sensory Reweighting for a Woman with Persistent Mal de Debarquement: A Case Report(2015) Liphart, JodiBackground and Purpose: Persistent mal de debarquement is an uncommon disorder occurring after a sea voyage, or a plane or train trip. Symptoms include unsteadiness, rocking sensation, visual motion intolerance, cognitive slowing, and excessive fatigue. It is thought to be a result of faulty multisensory adaptation. The purpose of this case report was to describe the use of sensory reweighting, a therapeutic approach aimed at reweighting the balance between the 3 sensory systems, to decrease symptoms and increase functional abilities of a woman with persistent mal de debarquement. Case Description: A 69-year-old woman with a 4-year history of persistent mal de debarquement after a plane trip reported a constant feeling of rocking, unsteadiness, and a loss of balance in low lighting or visually rich environments. She experienced a previous fall and had limited her social activities because of her symptoms. Interventions: Sensory reweighting therapy was administered twice a week for 10 weeks. Activities included balance training using vestibular, somatosensory, and visual challenges to vary the sensory input available. Outcomes: A 5-point increase was observed on the Berg Balance Scale, she doubled her balance time in tandem stance position, and improved from moderate to low impairment on the Dizziness Handicap Inventory. She had a significant change on the Global Rating of Change Scale. Subjectively, she felt she had improved 50% and was less disabled. Discussion: A rehabilitation approach aimed at sensory reweighting improved this patient's function and community reintegration. Her symptoms were reduced and stability and balance improved.