Division Of Nerve Research Articles

A rare case of a pleomorphic adenoma of the submandibular gland

We report the case of a 27-year-old female with a painless slowly growing mass that had developed over 2 years in the right submandibular region. Physical examination revealed a firm painless submandibular mass. Fine-needle aspiration and computed tomography (CT) scan concluded a pleomorphic adenoma of the submandibular gland. The patient underwent a right total submandibular sialoadenectomy. Histopathological examination confirmed the diagnosis of pleomorphic adenoma arising from the submandibular gland. Transient palsy of the marginal mandibular division of the facial nerve was noted post-operatively, which recovered with supportive management. Pleomorphic adenoma of the submandibular gland represents a diagnostic and therapeutic dilemma in young adults. Preoperative evaluation, including MRI/CT scan and fine-needle aspiration, is recommended in all cases. Total submandibular sialoadenectomy is the standard recommended treatment to minimise recurrences and avoid malignant transformation.

Focused gluteal region dissection on the human sciatic nerve

Dissection provides an understanding of human anatomy that is difficult to achieve solely with the use of textbooks. The knowledge obtained from anatomical dissection has allowed medical practitioners the ability to understand the anatomy that forms that basis of a particular clinical presentation, and more effectively treat the condition. These conditions include piriformis syndrome and sciatica. Clinical conditions may also arise due to anatomical variations which are rare presentations, absences, or arrangements of structures. The ultimate goal of the dissection in this report was to discern the pathway of the sciatic nerve and its divisions. In this report, the dissection of the gluteal region of a left leg from a female cadaver is detailed. The findings reveal two anatomical variations, a high division of the sciatic nerve and a muscular slip lateral to the long head of the biceps femoris. Additional research is needed to determine the implications of these anatomical variations in the clinical context. This prosection will be an important educational resource for future students, and could not have been possible without the generous donors.

Deep peroneal neuropathy induced by prolonged squatting: a case report.

Prolonged squatting is a well-documented cause of common peroneal neuropathy, wherein the common peroneal nerve is thought to be compressed between the biceps femoris tendon and the lateral head of the gastrocnemius muscle or the fibular head. However, deep peroneal neuropathy resulting from prolonged squatting has not been previously reported. We present the case of a tile installer who developed unilateral deep peroneal neuropathy following extended squatting, diagnosed through ultrasonography, which identified the bilateral division of the common peroneal nerves between the knee joint and the fibular head. This case underscores the value of ultrasonography, particularly when electrodiagnostic results are inconsistent with clinical expectations.

A Retrospective Analysis of Medical Management Strategies for Trigeminal Neuralgia: An Institutional Review.

Background Neuropathic pain results from nervous system damage, and trigeminal neuralgia (TN), also called tic douloureux, is a chronic disorder affecting the trigeminal nerve. TN causes sudden, severe, recurring facial pain that can be highly disabling. Treatment usually involves medications like carbamazepine, oxcarbazepine, gabapentin, or baclofen to manage nerve pain. If medications are ineffective, surgical interventions like microvascular decompression or gamma knife radiosurgery may be explored for symptom relief. Aim and objectives This study aims to assess the demographic characteristics and clinical features of patients with TN treated at a private institution. The objective was to assess key demographic factors, including age, gender, and the affected trigeminal nerve divisions, with a focus on identifying the most frequently involved nerve divisions in TN cases. Methodology This five-year retrospective study (January 2019-April 2023) in the Oral Medicine and Radiology Department analyzed 483 TN cases, including 300 patients with confirmed primary TN and complete records. Dental Information Archive System (DIAS) data covered demographics, clinical features, treatments, and outcomes. Pain levels were assessed using the visual analog scale (VAS). LFTs monitor the long-term effects of medications like carbamazepine. Statistical analysis employed descriptive statistics, chi-square tests, and t-tests, with p < 0.05 considered significant. Results Of 7,500 outpatients in the Oral Medicine Department, 483 were diagnosed with TN, and 300 met the diagnostic criteria for inclusion in a five-year study (January 2019-April 2023). The average age was 60 years for men and 58.5 years for women. TN primarily affected the right side in 158 patients (56%), while the left side was involved in 114 (43%) of the cases (p = 0.04) and most commonly involved the maxillary nerve (V2) in 159 patients (53%) and the mandibular nerve (V3) in 141 patients (47%), with a slight female predominance (p = 0.02). One hundred thirty-five patients (45%) used carbamazepine alone, while 84 were treated with carbamazepine and gabapentin, and 81 were treated with carbamazepine and baclofen. The combination of carbamazepine and gabapentin was the most effective, achieving pain control in 123 patients (75%) compared to 94 patients (70%) with carbamazepine alone and 119 patients (72%) with carbamazepine and baclofen (p = 0.06). VAS scores showed better pain relief with carbamazepine and gabapentin (VAS: 3.8 ± 1.0), carbamazepine alone (mean VAS: 4.5 ± 1.2) and carbamazepine with baclofen (mean VAS: 4.2 ± 1.1). In long-term management, 45 patients (15%) discontinued due to side effects, while 105 patients (35%) continued on carbamazepine alone, 90 patients (30%) on carbamazepine with gabapentin, and 60 patients (20%) on carbamazepine with baclofen (p = 0.04). LFTs were performed on 240 patients (80%), while 60 patients (20%) did not undergo LFTs. Conclusions This study underscores the treatment of TN, with anticonvulsants as the primary therapy and alternative options available for refractory cases. However, limitations like small sample size and lack of long-term follow-up affect the findings' generalizability. The results highlight the importance of treatment plans and the potential advantages of combination therapies in clinical practice.

ANATOMICAL VARIATIONS IN A FINITE ELEMENT NERVE MODEL OF THE HUMAN FOOT

The nerves in the foot offer a significant role in controlling the movement and correct loading of the foot by providing continuous feedback to the central nervous system. The health importance in the anatomical variations of nerves, such as the locations, the lengths, the communicating branches, and the distance between the adjacent nerve terminals between individuals have given prominence to anatomists as well as physiologists. A previously developed one-dimensional (1D) model of the nerve was extended to determine different anatomical variations in the nerves of the foot, as a realistic anatomical-based variant nerve model of the human foot is not available. The model was verified against experimental data from the literature for communicating branches and distances of various area of the human foot. For instance, the simulated distances of the communicating branches of the plantar nerves and medial dorsal cutaneous nerve (MDCN) division proximal to the first digital space were found to be 43.3 mm and 112.3 mm, respectively, which was in general agreement with the experimental distances of 8-56 mm and 96-116.74 mm, respectively. The developed nerve variant model provides a platform for future studies of the various geometrical and efficient concerns of neurovascular diseases such as diabetic neuropathies by determining the parameters of nerve conduction studies.

Lingual nerve revisited-A comprehensive review Part II: Surgery and radiology.

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal nerve, arising in the infratemporal fossa. It provides sensory fibers to the mucous membranes of the floor of the mouth, the lingual gingiva, and the anterior two-thirds of the tongue. Although the LN should rarely be encountered during routine and basic oral surgical procedures in daily dental practice, its anatomical location occasionally poses the risk of iatrogenic injury. The purpose of this section is to consider this potential LN injury risk and to educate readers about the anatomy of this nerve and how to treat it.

Lingual nerve revisited-A comprehensive review Part I: Anatomy and variations.

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal. It primarily carries sensory fibers from the lingual gingiva, mucous membranes of the floor of the mouth, sublingual gland, and the anterior two-thirds of the tongue. Recent studies have explored and reclassified the five branches of the LN as branches to the isthmus of the fauces, lingual branches, sublingual nerves, posterior branch to the submandibular ganglion, and branches to the sublingual ganglion. The knowledge of the LN anatomy and its variants is clinically relevant to avoid its injury during oral procedures. The objective of this paper is to review the literature on the LN and to describe the anatomy, its course, and its functions.

High-Resolution Magnetic Resonance Neurography at 7T: A Pilot Study of Hand Innervation.

The emergence of 7T clinical MRI technology has sparked our interest in its ability to discern the complex structures of the hand. Our primary objective was to assess the sensory and motor nerve structures of the hand, specifically nerves and Pacinian corpuscles, with the dual purpose of aiding diagnostic endeavors and supporting reconstructive surgical procedures. Ethical approval was obtained to carry out 7T MRI scans on a cohort of volunteers. Four volunteers assumed a prone position, with their hands (N = 8) positioned in a "superman" posture. To immobilize and maintain the hand in a strictly horizontal position, it was affixed to a plastic plate. Passive B0 shimming was implemented. Once high-resolution 3D images had been acquired using a multi-transmit head coil, advanced post-processing techniques were used to meticulously delineate the nerve fiber networks and mechanoreceptors. Across all participants, digital nerves were consistently located on the phalanges area, on average, between 2.5 and 3.5 mm beneath the skin, except within flexion folds where the nerve was approximately 1.8 mm from the surface. On the phalanges area, the mean distance from digital nerves to joints was approximately 1.5 mm. The nerves of the fingers were closer to the bone than to the surface of the skin. Furthermore, Pacinian corpuscles exhibited a notable clustering primarily within the metacarpal zone, situated on the palmar aspect. Our study yielded promising results, successfully reconstructing and meticulously describing the anatomy of nerve fibers spanning from the carpus to the digital nerve division, alongside the identification of Pacinian corpuscles, in four healthy volunteers (eight hands).

Herpes Zoster Ophthalmicus: Presentation, Complications, Treatment, and Prevention.

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4-20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO.Graphical abstract available for this article.

Uncommon presentation of orbital myositis following herpes zoster ophthalmicus

Herpes zoster ophthalmicus (HZO) is a manifestation of the reactivation of the varicella zoster virus, characterised by vesicular rash along the ophthalmic division of the trigeminal nerve. A rare but significant complication of HZO is orbital myositis, marked by painful swelling of extraocular muscles and periorbital tissues. We present the case of a 72-year-old woman initially presenting with ophthalmological symptoms, notably conjunctival congestion and superficial punctate keratitis, preceding the typical vesicular rash of herpes zoster. The subsequent development of diplopia led to the detection of lateral rectus palsy. Neuroimaging revealed orbital myositis, with the patient showing marked improvement following treatment with oral steroids. This case emphasize the importance of recognizing orbital myositis as a complication of HZO.

Pterygoideus proprius muscle: stuck between the greater wing and lateral pterygoid plate.

The muscles of mastication derive from a common embryological source, and the presence of accessory muscles in the infratemporal fossa (ITF) is uncommon. Here, we present findings from postmortem dissection of the ITF revealing a unilaterally present muscle extending from the greater wing of the sphenoid to blend inferiorly with the medial and lateral pterygoid muscles before attaching to the lateral pterygoid plate. This muscle is most consistent with the pterygoideus proprius muscle initially described in 1858. Though the exact embryological origin and function of this muscle remain speculative, these topics are nonetheless worth investigating as it may provide insight regarding the ontogeny of muscles descending from the first pharyngeal arch. Additionally, presence of the pterygoideus proprius muscle may have clinical implications and impact surrounding structures such as the mandibular division of the trigeminal nerve, maxillary artery, pterygoid venous plexus, masticatory muscles, and temporomandibular joint (TMJ).

A transmuscular path of the medial branch of the high division of the median nerve: an anatomical variation of clinical and surgical importance

The median nerve (MN) is a mixed nerve formed in the brachial plexus, which innervates a large part of the upper limb. It presents several variations in its trajectory, resulting in many pathologies and iatrogenic surgical compromises. This report highlights a transmuscular route of the medial branch of the upper division of the MN, which to date does not fit into the classifications described in the literature on MN variations. Knowledge of this high division of the MN, as well as its transfixation by the flexor digitorum superficialis muscle, is of fundamental importance in neuropathy syndromes due to entrapment of the MN, as well as in surgical guidance to prevent injuries. Late diagnosis of traumatic peripheral nerve injuries results in greater functional impairment and greater socioeconomic loss, especially in young patients. Therefore, timely identification is essential to minimize long-term consequences and improve the patient's quality of life.

MR-Neurography of the facial nerve in parotid tumors: intra-parotid nerve visualization and surgical correlation.

One of the most severe complications in surgery of parotid tumors is facial palsy. Imaging of the intra-parotid facial nerve is challenging due to small dimensions. Our aim was to assess, in patients with parotid tumors, the ability of high-resolution 3D double-echo steady-state sequence with water excitation (DE3D-WE) (1) to visualize the extracranial facial nerve and its tracts, (2) to evaluate their relationship to the parotid lesion and (3) to compare MRI and surgical findings. A retrospective study was conducted including all patients with parotid tumors, who underwent MRI from April 2022 to December 2023.Two radiologists independently reviewed DE3D-WE images, assessing quality of visualization of the facial nerve bilaterally and localizing the nerve's divisions in relation to the tumor. MRI data were compared with surgical findings. Forty consecutive patients were included (M:F = 22:18; mean age 56.3 ± 17.4years). DE3D-WE could excellently visualize the nerve main trunk and the temporofacial division in all cases. The cervicofacial branch was visible in 99% of cases and visibility was good. Distal divisions were displayed in 34% of cases with a higher visibility on the tumor side (p < 0.05). Interrater agreement was high (weighted kappa 0.94 ± 0.01 [95% CI 0.92-0.97]). Compared to surgery accuracy of MRI in localizing the nerve was 100% for the main trunk, 96% for the temporofacial and 89% for the cervicofacial branches. Facial nerve MR-neurography represents a reliable tool. DE3D-WE can play an important role in surgical planning of patients with parotid tumors, reducing the risk of nerve injury.

Morphology of the obturator nerve, an anatomical study with emphasis on its clinical implications

Background The goal of this cadaveric cross sectional study was to analyse the branching pattern of the obturator nerve morphologically and to determine its dimensions in embalmed cadavers. Methods In this cross sectional study, we examined 50 embalmed adult cadaveric lower limbs. Sex was not taken into consideration in the analysis; however, a side-based comparison was performed. The measurements were performed using a digital Vernier caliper. Results The branching of obturator nerve was observed at the pelvic cavity in 28 specimens (56%) and inside the obturator canal in 12 specimens (24%). The division of obturator nerve wasn’t observed in 10 specimens (20%). The length, width and thickness of the trunk of obturator nerve was 108.26 ± 9.53 mm, 2.84 ± 0.88 mm and 1.11 ± 0.35 mm. The width and thickness of the anterior and posterior divisions of obturator nerve measured 2.19 ± 0.82 mm, 0.9 ± 0.1 mm, 0.99 ± 0.6 mm and 0.71 ± 0.26 mm. The topography of branching of obturator nerve from the superior and inferior border of the obturator foramen was located at 1.48 ± 0.58 mm and 3.07 ± 1.1 mm away. The length of anterior division of the obturator nerve measured 110.88 ± 12.02 mm over the right side and 107.13 ± 7.81 mm over the left side. The width of the main trunk of obturator nerve was 2.87 ± 0.64 mm over the right side and 2.82 ± 0.64 mm over the left side. Conclusions We believe that morphometric data of the obturator nerve will be enlightening to the operating surgeon during procedures such as obturator nerve block, nerve transplantation, and obturator nerve repair. The dimensions of the obturator nerve observed in the present study can be utilized as a morphological database for our sample population.

Injury and Biological Factors Impact Shoulder Function following Autogenous Grafting of Spinal Nerves for Pan-Brachial Plexus Reconstruction.

Shoulder function following spinal nerve grafting in pan-brachial plexus injuries(Pan-BPI) is not well described. The purpose of this study was twofold: 1)to evaluate shoulder abduction(ABD) and external rotation(ER) after grafting of viable spinal nerves to the suprascapular nerve(SSN), axillary nerve(AxN), or posterior division of the upper trunk(PDUT); and 2)to determine patient characteristics, injury severity/characteristics, and nerve graft factors that influenced outcomes. 362 Pan-BPI reconstruction patients from a single institution were reviewed for those who underwent spinal nerve grafting for shoulder reanimation between 2001 and 2018. Patient demographics, injury severity scores(ISS), graft characteristics, strength, range of motion for shoulder ABD and ER, and patient-reported outcomes were recorded. Patients were divided into three groups based on the recovery of shoulder function: no return, ABD only, and ABD and ER. 110 patients underwent spinal nerve grafting, with 41 meeting inclusion criteria. 17(41.5%) had no return of shoulder function, 14(34.1%) had ABD alone, and 10(24.4%) had ABD and ER. Patients with recovery of both ABD and ER were significantly younger(18.6±5.56), had lower BMI(22.4±4.0), and lower ISS(10.5±6.24, p=0.003). Multivariable analysis found that with increasing age(OR:0.786, 95%CI:0.576,0.941) and ISS(OR:0.820, 95%CI:0.606-0.979), odds for return of ABD and ER significantly decreased. In Pan-BPI, 24.4% of patients demonstrated return of both ABD and ER following spinal nerve grafting to SSN and either AxN or PDUT. Age, BMI, and ISS were associated with poorer recovery of shoulder function. Careful patient selection and consideration of age, BMI, and ISS may improve outcomes of spinal nerve grafting for shoulder reanimation. III.

453 Changed Innervation Upon Loss of Mandibular Division of Trigeminal Nerve to Muscles of Mastication

INTRODUCTION: The gastrulation brain homeobox (Gbx) genes are essential for patterning and maintenance of neurons along the anteroposterior axis of the developing neural tube. Knockout (ko) of Gbx2 results in neonatal lethality associated with neurological and other defects. To understand pathologies, ko studies are not realistic as gene loss usually results in death before birth. Gbx2 neo/neo mutant mice express 6-10% of the wildtype Gbx2 expression levels. They have milder malformations than ko mice but lack the cerebellar vermis and mandibular division of the trigeminal nerve (3rd division of 5th cranial nerve = V3), among other defects. These Gbx2 neo/neo mutant mice die perinatally as they are unable to suckle due to lack of motor innervation via V3 to the muscles of mastication. Muscle cells develop largely without interaction with their motor nerve. However, the final differentiation of myocytes requires interactions with nerve fibers. Unexpectedly, the muscles of mastication appear normal in Gbx2 neo/neo mutant mice, despite the lack of V3. METHODS: We performed microdissections of neonate wildtype and Gbx2neo/neo mutant mice. Additionally, we embedded mutant and wildtype mouse embryos in paraffin, serial sectioned them (7 μm), stained the sections with Azan staining, and analyzed specimen microscopically. RESULTS: Current analysis of the data to identify where nerve fibers in the muscles of mastication originate is in process. We favor the origin of these fibers from the facial nerve (7th cranial nerve), which has several overlapping territories with the trigeminal nerve. CONCLUSIONS: Muscles require innervation for their final differentiation steps. The loss of a nerve can result in the invasion of another nerve into the territory of the lost one, which rescues muscle differentiation but not muscle function. IACUC Ziermann Med-20-02, Funding NSF #2000005 to Ziermann.

Gamma Knife radiosurgery for the treatment of trigeminal neuralgia: A single center-experience

Introduction and objectivesWe aimed to assess the outcomes of patients with trigeminal neuralgia (TGN) who underwent Gamma Knife radiosurgery (GKRS). Materials and methodsFifty-three patients with typical TGN underwent GKRS from May 2012 until December 2022. Among these patients, 45 patients who were follow-up for at least 12 months were included in the study. A mean dose of 87.5 Gy (range, 80–90) was administered to the trigeminal nerve. Postoperatively, outcome was considered excellent if the patient was pain- and medication-free. ResultsThe mean symtpom duration was 9.53 years, and the mean patient age was 59.8 years (range, 34–85). The mean follow-up period was 46.8 months (range, 12–127 months). 46.7% of patients had a history of previous surgical interventions. A single nerve division was affected in 14 patients (31.1%), and multiple divisions were affected in 31 patients (68.9%). The rate of initial pain relief was 80%. Hypoesthesia in the area of trigeminal nerve developed in 30 (66.7%). Twenty patients (44.4%) exhibited excellent results within 72.4 months. Recurrence occurred in 11 patients (24.4%) with 27.6 months. ConclusionsOur results suggest that GKRS is a safe and effective procedure. Thus, it is an attractive first- and second-line treatment choice for TGN.

A Systematic Review and Meta-Analysis on the Impact of Preserving the Hepatic Branch of the Vagus Nerve in Upper Gastrointestinal Surgeries

Background: Upper gastrointestinal surgeries encompass procedures on the esophagus, stomach, liver, pancreas, and gallbladder. To access the surgical area, it is standard to dissect the hepatogastric ligament, transecting the hepatic branch of the vagus nerve contained within it. Yet, the hepatic branch, which innervates the liver and gallbladder, contributes to digestion, bile secretion, and glucose metabolism. Hence, recent surgical studies have explored the potential benefits of hepatic branch preservation in comparison to non-preservation. This systematic review and meta-analysis endeavors to compile and analyze the outcomes of these studies. Methods: PubMed, EMBASE, Scopus, and Cochrane, were searched for cohort studies and randomized control trials comparing hepatic nerve preservation and division during upper gastrointestinal surgery in adults, up to April 2023. Two independent reviewers evaluated abstracts and full-text reviews, extracted pertinent information, and conducted risk-of-bias assessments using the RoB 2 and Newcastle-Ottawa instruments. Results: Thirteen studies involving 3001 participants were included for meta-analysis. Hepatic branch preservation was linked to a decrease in appetite loss (OR 0.04, 95% CI 0.01-0.18), reflux symptoms (OR 0.16, 95% CI 0.06-0.43) and gallstone formation (OR 0.25, 95% CI 0.09-0.69). However, preservation was associated with an increased incidence of Clavien-Dindo Grade 2 complications (OR 1.73, 95% CI 1.01-2.96) in gastrectomies. Conclusion: Hepatic branch preservation is associated with favorable post-surgical metabolic outcomes, notably appetite preservation. This may be due to the hepatic branch’s role in facilitating brain-liver crosstalk, thus, influencing homeostatic processes like appetite control and glucose metabolism. Reduced gallstone incidence is likely due to preservation of gallbladder motility and function, achieved through retention of parasympathetic innervation.

Pain Relief-Related Structural Brain Alterations in Trigeminal Neuralgia Induced by Noninvasive Stereotactic Radiosurgery: A Pilot Study

PurposeTrigeminal neuralgia (TN) is a devastating chronic pain disorder, defined by unilateral shock like pain in at least one division of the trigeminal nerve. Although several studies have investigated structural brain plasticity in TN patients, treatment-induced alterations remain largely uninvestigated. Materials/MethodsCombining T1-weighted magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) and multiple-regression analyses, we assessed gray matter maps of TN patients to investigate changes in gray matter volume (GMV) from before to half a year after stereotactic radiosurgery (SRS). ResultsComparing pre- and post-GMV of 25 TN patients (16 females; mean age 67 years) did not yield any significant clusters, suggesting that the impact of SRS intervention itself on gray matter structure may be negligible. In relation to SRS-induced pain-relief, we found a significant GMV increase in the left superior frontal gyrus associated with greater degrees of pain relief (p=0.024), and a trend toward an increase in GMV in the left dorsolateral prefrontal cortex (p=0.097). ConclusionIn this pilot study, we observed significant increases of GMV in the left superior frontal gyrus with SRS-induced improvements in pain, and a trend for the dorsolateral prefrontal cortex. Future studies are indicated to validate these findings and determine whether SRS-induced decrease in distracting pain events and subsequent increases in GMV result in improved functionality, decreased dependence on "top-down" control, and improved cognitive/executive balance with amelioration of pain events.

Laws of Pathophysiology of Migraine in the Third Millennium

Science is the art of systematic and reproducible measurements, ultimately leading to knowledge supported by a holistic logic. Besides serendipity, there are 6 ways in general to obtain knowledge: authoritarianism; mysticism; rationalism, empiricism; pragmatism; and scepticism. Over the last 100 years, a canonical mythology – cortical spreading depression (CSD) – has prevailed in migraine pathophysiology. Conversely, a well-defined adaptive/protective role has evolved for CSD in locusts, Drosophila, and mammals. Additionally, an elaborate but entirely symptomatic nosologic system has arbitrarily evolved in migraine / primary headache. While the so-called systematic but symptomatic classification system of migraine / primary headache keeps on advancing the data-bank exponentially, the cause-effect nexus continues to obscure the most important systematic and insightful components of the knowledge of primary headache. The first step in advancing the cause-effect mystery of migraine / primary headache is to create a conceptual, consistent, and important adaptive-pathogenetic divide in the massive and disparate data-linked pathophysiology of the disorder. Once certain definitive principles (not laboratory/neuroimaging / genetic/epidemiologic data) emerge in the science of migraine / primary headache, we become empowered to understand the complex but key phenotypic blueprint as well as the neuro-pathophysiology / neuropsychiatry of the entity, including the visual (nasal visual-field sparing digitally-displaceable and eyeball-movement-synchronous scintillating scotomata), the lateralizing fronto-temporal-nuchal headache exclusively involving the ophthalmic division of the trigeminal nerve, and the associated features such as ‘stress’, ‘post-stress’, ‘autonomic storm’, ‘protean’ and ‘spontaneous’ onset and offset, and headache-aborting nausea-vomiting. In this manner, we have also evolved principles to begin to understand the most complex female predominance of migraine patients in adults [F:M=3:1] as well as the decline of prevalence in migraine attacks following menopause and advancing age. The Laws of the Pathophysiology of Migraine encompass the invaluable neurological / neuro-ophthalmological shift in pathophysiology from the brain to the eye.