Epilepsy over the centuries: a disease survived at the time.

In this study, we have made a historical review of epilepsy through the centuries, from pre-Christian era to the present time. The epileptic was examined by Hippocrates, the first to recognize epilepsy as a disease and not as a supernatural manifestation called Morbus Sacer. The dark years of the Middle Ages were the worst for the disease, where the sufferer was even subjected to torture. The period of the Renaissance saw the epileptic isolated from society while the Enlightenment century improved the knowledge about the disease, thanks also to the first autopsies that showed post traumatic neurological lesions. However, some stigmata of the disease that prevented the marriage of epileptics persisted. It was the prelude to the years 1800-1900, characterized by Lombrosian concepts and Nazi convictions. Lombroso included epileptics among delinquents and criminals, identifying them as such on the basis of physical alterations. Nazi racism introduced the concept of eugenics excluding the epileptic from the so-called pure race. Today, epilepsy is considered a treatable neurological disorder. Morbus Sacer belongs to a remote past.

A singular association of migraine with brainstem aura and Alice in Wonderland syndrome.

BACKGROUND: In this work, we describe an association of brainstem headache with aura (BHA) and Alice in Wonderland syndrome (AIWS) in a 17-year-old male, suffering from crises of vertigo, weakness, dysarthria, and diplopia, in half-hour duration, followed by diffuse or occipital headache, lasting several hours. METHODS: The frequency of the attacks was monthly, and once there was short loss of consciousness. The last episodes were accompanied by symptoms such as deformation of figures and objects, small or large in shape. RESULTS: Diagnostic examinations were performed, mainly neuroimaging tests such as brain MRI and brain angio-MRI, all resulting normal; and treatment with flunarizine was followed by improvement of both BHA and AIWS symptoms. CONCLUSIONS: There would be a correlation between BHA and AIWS, presumably represented by dysfunction of temporo-parieto-occipital carrefour.

Occipitocervical Fusion.

Occipitocervical fusion is a surgical technique in continuous evolution due to the innovation of devices, operative and instrumentation techniques. The aetiologies responsible for occipitocervical instability are trauma, neoplastic disease, metabolic disease or congenital disease. A variety of stabilization techniques are currently available depending on the type of patient and surgeon's experience. Each of these techniques requires thorough knowledge of the anatomy of the craniovertebral junction.

Occipital Nerve Stimulation for Refractory Pain after Occipitocervical Fusion.

Occipital nerve stimulation (ONS) is electric stimulation of the distal branches of the greater occipital nerve by cylindrical or paddle leads implanted in subcutaneous occipital tissue. This surgical option has emerged as a promising treatment for different types of disabling medical refractory headache and recently also for residual occipital and nuchal pain after previous occipitocervical fusion. The mechanisms of action have not yet been clearly explained: electrical stimulation of the occipital nerve has both peripheral and central effects on the nervous system, which may modulate nociception. ONS is a well-tolerated and safe procedure in comparison with other invasive modalities of treatment. Lead migration/dislodgement is a common complication, but use of new surgical techniques and leads may reduce the rate of this complication.

Cortical neuromodulation for neuropathic pain and Parkinson disease: Where are we?

Cortex neuromodulation is promising approach for treatment of some neurological conditions, especially neuropathic pain and Parkinson's disease. Effects of non-invasive cortical stimulation are short lived; transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) may be useful to assess the suitability for invasive cortical stimulation. Direct cortical stimulation (DCS) is the method able to provide long-lasting effects in treatment of neuropathic pain and some symptoms of Parkinson's disease through the use of totally implantable systems that ensure a chronic stimulation.

Nonsurgical lumbar radiculopathies treated with ultramicronized palmitoylethanolamide (umPEA): A series of 100 cases.

In this clinical/observational study we have reported the administration of Palmitoylethanolamide (PEA) in patients suffering from radicular lumbar spinal pathology, who had no indication for surgical treatment. We analyzed a series of 100 cases retrospectively, all undergoing clinical and diagnostic investigations, which had shown the presence of abnormalities of the vertebral body and intervertebral discs, mainly degenerative, such as spondyloarthrosis, spondylo-discarthrosis, disc protrusion, excluding disc herniation, which fell within surgical cases. We then administered ultramicronized PEA (umPEA) to these patients, in combination with paracetamol and codeine, obtaining interesting results regarding the improvement of pain symptoms of the spine pathology, in the various checks carried out, through the administration of pain assessment scales. We also noted its safety due to the total absence of adverse effects. The obtained results encourage the use of PEA in degenerative spine pathologies.

New-onset hemodialysis-related headache presenting as migraine aura.

Hemodialysis headache (HDH) is an infrequent new-onset symptom, occurring mainly in old uremic patients. Type of pain is nonspecific, occurs during hemodialysis treatment, assuming features similar to tension-type headache and representing a problem, also as regards the therapy to be taken. International Headache Society (IHS) has placed this form of headache among the headaches disorders of homeostasis. We found a case of new-onset HDH in old uremic man, presenting with migraine aura features. A similar case has not been reported in literature, placing us some questions: why and how does this happen? What are the mechanisms involved? Role of trigeminal-vascular system and cortical spreading depression as regards the aura could be considered, through the activation of neuroinflammatory events, lastly causing migraine aura. Moreover, the administration of flunarizine strongly improved migraine symptoms in our patient, as happens in migraine syndromes. Definitely, this case leads us to think that some mechanisms involved in headaches will need to be further clarified.

Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.

Src family kinases (SFK) are a group of non-receptor tyrosine kinases which play a pivotal role in cellular responses and oncogenesis. Accumulating evidence suggest that SFK also act as a key component in signalling pathways of the central nervous system (CNS) in both physiological and pathological conditions. Despite the crucial role of SFK in signal transduction of the CNS, the relationship between SFK and molecules implicated in pain has been relatively unexplored. This article briefly reviews the recent advances uncovering the interplay of SFK with diverse membrane proteins and intracellular proteins in the CNS and the importance of SFK in the pathophysiology of migraine and neuropathic pain. Mechanisms underlying the role of SFK in these conditions and potential clinical applications of SFK inhibitors in neurological diseases are also summarised. We propose that SFK are the convergent point of signalling pathways in migraine and neuropathic pain and may constitute a promising therapeutic target for these diseases.

Percutaneous intradiscal injection of radiopaque gelified ethanol: short- and long-term functional outcome and complication rate in a consecutive series of patients with lumbar disc herniation.

Lumbar disc herniation (LDH) is a common cause of low back pain (LBP) and/or radicular pain (RP). Over the years, different therapies have been proposed to treat symptomatic LDH, including different minimally invasive techniques and open surgical methods. Recently, percutaneous intradiscal injection of radiopaque gelified ethanol (RGE) DiscoGel® has emerged as an effective therapeutic option in patients with LDH. Nevertheless, only few studies addressed the reliability of this technique. The purpose of this study was to evaluate the efficacy and safety of this procedure. We analysed surgical and outcome data of patients with small or medium LDH treated by DiscoGel between 2012 to 2015. Outcome variables included pain relief, the limitation on physical activity and severity of depression status. Overall, complication rate was defined as the occurrence of any perioperative adverse events. A total of 94 consecutive patients were enrolled in the study. Pain relief was achieved in 90.6% and 88.8% of patients at 1- and 4-year follow-up, respectively. At the last follow-up, at least a satisfactory result was achieved in 92.5% of patients. Similar results were obtained in the limitation on physical activity. Depression status did not significantly change after treatment. There was no mortality, and no patients experienced permanent sequelae. In well-selected patients, DiscoGel has proved effective in maintaining excellent functional results in terms of pain relief and limitation on physical activity while minimizing the overall rate of complications related to these kinds of surgical procedures.

The Legacy of Rita Levi-Montalcini: From Nerve Growth Factor to Neuroinflammation.

Rita Levi-Montalcini was an extraordinary personality and with her profession she made a tremendous contribution to humanity. Doctor, Nobel laureate for medicine, neuroscientist, she contributed, thanks to her research, to improve the knowledge of the nervous system. She discovered the nerve growth factor, which is applied in various fields of neurology, concerning neurodegenerative diseases. She also studied, in relatively newer years, the mechanisms of neuroinflammation. This last is a research that has been developing in recent years and is based on the predominantly anti-inflammatory properties of endogenous substances that able to act not only on diseases of the nerves, neuropathies, on the nerve roots, and radiculopathies but also on migraine and other non-neurological diseases. Her long life was full of positive and negative events. Born in a Jewish family, she lived her life as a young woman through war, Nazi deportations, and the Holocaust. Despite the difficulties, she found time to do research in the medical field, organizing research laboratories with other scholars. She had a difficult life, interspread with pain, destruction, extermination of human beings but also rewarded by scientific discoveries. A "small" woman but a great neuroscientist.

Cardiac myxoma and neural crests: a tense relationship.

In cardiac myxomas, the malignant transformation process, selecting incidental gene mutations and leading to loss of proliferation control, has not a so drastic effects in terms of growth rate of tumor mass, but frequently the particular location of lesion engrosses the high risk for health. For accurate cancer cell profiling, it is important to establish the embryologic origin of malignant cells and their initial commitments, above all, in the sight of therapeutic strategies and solutions. Here, we advance, for cardiac myxoma, the hypothesis of an origin from cardiac neural crest cells and we attempt to support it by an integrated discussion of current knowledge about embryological characteristics of neural crest cells and most recent studies focusing cardiac myxomas. We discuss the relationship between the basic plasticity of cardiac neural crest cells and some typical mutations arising in neoplastic lesions as well as the expression of typical cell markers of neural crests derivatives. Dysfunctions in proliferative and migratory programs, focused in other studies, are evaluated in the context of the topological and histopathological characteristics of cardiac myxomas.

Deep brain stimulation for treatment-resistant depression: a safe and effective option.

Introduction: Major depressive disorder (MDD) is the leading cause of years lost to disability worldwide. Pharmacotherapy and psychotherapy are effective treatments in most depressive episodes; but, about 30% of MDD patients remain symptomatic, and relapse is a common event. Recently, deep brain stimulation (DBS) has emerged as a valid therapeutic option in treatment-resistant depression (TRD) patients.Areas covered: In this paper, the authors summarize the findings of studies focused on these pathophysiologic phenomena and specifically on the role of DBS as a therapeutic option in TRD patients. The authors simply reviewed RCTs, open-label studies, neurophysiological mechanisms of DBS in MDD, and the possible role of different targets. Finally, we suggest possible future options.Expert opinion: Depression is a systems-level disorder, involving several brain structures. Neuroimaging studies demonstrate multiple interconnected regions that modulate different neural networks. DBS can modulate different targets, and others are under investigation. Among these subcallosal cingulate gyrus (SCG), ventral capsule and ventral striatum (VC/VS) seems to be the most relevant targets. We believe that, in the next future, DBS for TRD might become a first-line of treatment, especially using directional leads, that may help us to improve therapeutic effects.

When History Meets Neurology: Neurological Diseases of Famous People.

This retrospective review focuses on some illustrious personalities of history, who have suffered from neurological illnesses. Neurological diseases represent about 10% of all illnesses, and therefore do not spare anyone, much less, famous people. In this review, we discuss the neurological disorders that have struck some celebrities throughout history. We briefly examine the lives of emperors, writers, poets, and musicians that have suffered from neurological diseases such as epilepsy, stroke, tumors, and other illnesses, and which caused death or disability. From a historical point of view, recollection of the lives of famous people afflicted by neurological disorders holds important lessons for future generations.

Suspected Pulmonary Embolism after Oxygen-Ozone Therapy for Low Back Pain.

Oxygen-ozone therapy is used to treat degenerative pathology of the spine when surgery is not needed (e.g., removal of a herniated disk). Some authors have described it as a safe and effective procedure in ∼ 70 to 90% of patients. The aim of the therapy is to dehydrate the intervertebral disk and alter its contents. However, this treatment has been associated with some rare but very serious side effects. Both cardiac damage and a case of fulminant septicemia were reported. We describe a case of suspected pulmonary embolism, followed by sudden death, in an elderly woman treated with oxygen-ozone therapy for lumbar pain caused by disk protrusion. We believe a massive pulmonary embolism occurred, probably caused by an intradiskal injection that accidentally punctured a venous vessel and created emboli.

Add-on administration of ultramicronized palmitoylethanolamide in the treatment of new-onset burning mouth syndrome.

AIM: The purpose of this study was to treat burning mouth syndrome (BMS) with a combination of painful gabapentin and ultramicronized palmitoylethanolamide (umPEA), in an attempt to improve the severe symptomatology of BMS. METHODS: We examined the case of a 60-year-old male, suffering from late-onset burning mouth syndrome. He found that gabapentin had a poor control of symptoms, thus we added umPEA, after administering a Visual Analog Scale (VAS), showing a score of 8-9. The patient also underwent laboratory examinations, neuroimaging exams such as brain CT/MRI and others, which all showed normal results. RESULTS: The result of combined therapy was satisfactory. After 3 months, the frequency and intensity of the pain had improved considerably, as demonstrated clinically and by VAS, with a score of 5. CONCLUSION: BMS is an oral pain-burning syndrome scarcely responsive to therapy. The most widely used medications are GABA-like substances, antidepressants, topiramate. In this case, we used PEA, which proved effective in the treatment of BMS, as well as in neuropathies and migraines.

What is the Current Role for Vitamin D and the Risk of Stroke?

INTRODUCTION: Increasing evidence supports the relationship between vitamin D and stroke. Vitamin D has now been proposed as a prognostic biomarker also for functional outcome in stroke patients. METHODS: A revision of the data suggests that low vitamin D is associated more with ischemic than with haemorrhagic stroke, even if the role of optimal vitamin D levels for vascular wall is still unclear. Vitamin D deficiency induces with different mechanisms an alteration of vascular wall. RESULTS: However, to date, the research supporting the effectiveness of vitamin D supplementation in stroke and in post-stroke recovery is still inadequate and conclusive evidences have not been published. CONCLUSION: In this review, we provide a better understanding of the role of vitamin D in stroke.

Cervical spinal cord compression from delayed epidural scar tissue formation around plate lead for SCS.

Cervical spinal compression is a serious and rare complication of spinal cord stimulation (SCS) that can occur using leads placed via open surgical approach. The present report describe a case of cervical plate lead implant that developed spinal and radicular compression symptoms after seven years due to the growth of fibrotic epidural mass at the level of lead. A review of literature is provided. A 59-year­old woman with 3-year history of left arm post­traumatic complex regional pain syndrome (CRPS) was treated with SCS performed with the implant of paddle lead in the epidural space from C3-C5. Seven years later she reported progressive paresthesia along the spine and the limbs, gait ataxia with sensation of weakness in the legs, increased muscle tone and tendon reflexes in the lower extremities and decrease in effectiveness of stimulation. Cervical CT showed a tissue mass into the cervical canal posteriorly to the lead. This finding was confirmed by MR performed after lead removal that also allowed to document the amount of spinal cord compression. The patient underwent C4-C5-C6 laminectomy and a thick scar was removed from the dura. After surgery there was progressive and incomplete improvement of neurological signs but symptoms related to algodystrophy recurred partly. The formation of hypertrophic epidural scar tissue at the level of lead implant must be taken into consideration in presence of the onset of progressive cervical myelopathy in patient treated with SCS using laminectomy lead.

Insular gliomas: a surgical reappraisal based on a systematic review of the literature.

INTRODUCTION: Insular gliomas are heterogeneous lesions whose management presents multiple challenges for their tendency to affect young patients in good neurological and cognitive conditions, their deep anatomic location and proximity with critical functional and vascular structures. The appropriate management of insular gliomas requires a multidisciplinary evidence-centred teamwork grounded on the best anatomic, neurophysiological and oncological knowledge. The present study provides a reappraisal of the management of insular gliomas based on a systematic review of the literature with the aim of guiding clinicians in the management of such tumors. EVIDENCE ACQUISITION: A systematic review of the literature from the Medline, Embase and Cochrane Central databases was performed. From 2006 to 2016, all articles meeting specific inclusion criteria were included. EVIDENCE SYNTHESIS: The present work summarizes the most relevant evidence about insular gliomas management. The anatomy and physiology of the insula, the new WHO 2016 classification and clinico-radiological presentation of insular gliomas are reviewed. Surgical pearls of insular gliomas resection as well as oncologic and functional outcomes after insular gliomas treatment are discussed. CONCLUSIONS: Management of insular gliomas remains challenging despite improvement in surgical and oncological techniques. However, the literature review supports a growing evidence that recent developments in the multidisciplinary care account for constant improvements of survival and quality of life.

Von Hippel-Lindau disease: when neurosurgery meets nephrology, ophthalmology and genetics.

INTRODUCTION: Von Hippel-Lindau (VHL) disease is a dominantly inherited condition associated with tumors in multiple organs, whose treatment requires heightened multidisciplinary teamwork. Therefore, a document summarizing all the pertinent knowledge is needed to enhance coordination of care. EVIDENCE ACQUISITION: A systematic review of the literature from the Medline, Embase and Cochrane Central databases was performed. From 1970 to 2017, all articles meeting specific inclusion criteria were included by at least one specialist physician for each field. EVIDENCE SYNTHESIS: We included 95 articles, mostly dealing with genetics or management of VHL associated tumors in one organ system. There were no papers discussing the manifestations of VHL altogether, which was the aim of our paper. CONCLUSIONS: VHL requires a multidisciplinary management to provide the highest quality of care. Coordination and communication between patients and caregivers is enhanced when knowledge is shared. Gathering together specialists in different domains around the production and reading of a comprehensive document such as the one hereby may contribute to this purpose.