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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.

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.

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.

Background. We describe the unusual case of a person suffering from lumbar pain, by herniated disc, treated with betamethasone. The abrupt suspension of the drug caused so called steroid withdrawal syndrome that may occur when receiving a glucocorticoid hormone for a long time it is abruptly stopped. Method. We administered it to a patient suffering from intense lumbar pain.The drug was suspended abruptly a few days after the onset of therapy. Results. The reaction to the suspension of the steroid was the onset of a severe migraine headache, which disappeared with the re-administration of betamethasone. Conclusions. What are the causal hypotheses of this event? An increase in endocranial pressure, of pseudotumor cerebri type? A case of delayed hypersensitivity, since the subject had already taken on betamethasone, without reporting any side effects? We think that the disorder is due to a condition of late hypersensitivity to the steroids, from unknown cause.

The prefrontal cortex is deputed to higher functions, such as behavior and personality. It includes three regions: ventromedial, orbitofrontal, and dorsolateral. Each of them has a function. Devising, programming, and planning are all conditions related to the dorsolateral cortex, also responsible for rational content and decision. Damage to this region results in apathetic syndrome, a condition that causes loss of interest, initiative, and attention, and in the most severe cases leads to a lethargic state. It is also known as a form of secondary depression, the so-called pseudo-depression syndrome, according to Karl Kleist or apathetic-abulic-akinetic syndrome, according to Alexander Luria. The prefrontal dorsolateral syndrome is responsible for the reduction or abolition of free will. Free will is an expression of individual freedom. It allows the human being to have and express own opinions as well as to respect those of others. Free will is related to moral sense, a binomial which directs the individual towards a proper social conduct. In this review, we describe the effects of the pseudo-depression syndrome on free will, of which we treat both the anatomical site and the social aspect.

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.

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.

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.

Background The surgical spinal degenerative pathology mainly concerns the herniated intervertebral disks. Surgery is indicated when the pain becomes chronic and intense, and when motor signs appear. The results are positive in about 90% of cases, leading to the solution of the problem. However, an estimated percentage of 4% to 20% reported residual pain and postural instability after the surgical treatment of discectomy. Method We have examined a sample of patients, retrospectively registered, undergoing surgical treatment for degenerative lumbar disease. Some of them developed postural instability. They were subjected to cycles of postural gymnastics. Postural gymnastics has proved to be a tool capable of solving unstable post-surgical posture. It included an exercise of breathing, one or two of muscular distension, one of muscular reinforcement, and one of postural correction. We used an evaluation form we created in agreement with the physiatrist for postural exercises that was based on some basic parameters such as muscle and respiratory function. At each cycle, a score was attributed to the performance of muscular and respiratory exercise to evaluate the function and therefore the degree of instability (1–3 = mild, 4–7 = medium, 8–10 = severe). Results Results were satisfactory, with return to normal posture. The improvement of postural instability has been demonstrated both by the score of the evaluation forms that have highlighted the transition from a state of severe intensity to one of normality and by a clinical aspect, concerning the static and dynamic posture. Conclusions The postural instability has a multifactorial genesis, and different mechanisms are involved: the vertebral bone structures and the pelvis, the paraspinal muscular structures, and the nerve structures. These structures are altered after surgery due to predisposing factors, and for the action of conditions acquired as obesity.

Hemangioblastomas (HBLs) are challenging vascular tumours with rare suprasellar location Surgery is recommended in patients with visual impairment, endocrine disorders or hydrocephalus. Surgical removal of pituitary stalk HBLs is challenging due to their location and high vascularity. Our narrative review was guided by the question: "what is the more suitable surgical approach to excise a suprasellar HBL?". Pertinent English literature was scrutinized from database inception to October 2016. Eighteen articles matched our selection criteria. Among the surgically treated patients, 4 were treated through a trans-sphenoidal (TS) approach, 13 through a transcranial approach (2 of them after TS failure). Five other cases were treated with radiotherapy (adjuvant in 3 cases) and 9 patients were managed with simple observation and/or medical treatment. We add a case of complete suprasellar HBL resection through an orbito-zygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC). To achieve satisfactory oncologic results with acceptable morbidity for symptomatic suprasellar HBLs, complete tumour removal with pituitary stalk sparing should be attempted through an OZ craniotomy with EAC that provides adequate exposure of the tumour, its vascular supply and the adjacent neural structures.

Palmitoyl ethanol amide (PEA) is an endogenous substance that plays a role in neuropathic pain. In this article, we evaluated both the safety and the efficacy of ultramicronized PEA (um-PEA) in the treatment of low back pain related to nonsurgical lumbar radiculopathy. In this prospective single-blind study, patients with low back pain related to nonsurgical lumbar radiculopathy received the fixed combination acetaminophen/codeine (500 mg + 30 mg/d) for 7 days, and then it was stopped and changed to um-PEA (1200 mg/d) for 30 days. Patients without an improvement in pain or disability started a second cycle of treatment with um-PEA (600 mg/d in tablets) for 30 days and then acetaminophen/codeine for 30 days. A total of 155 patients were included in the analysis. After the first cycle of treatment we recorded an improvement of pain in all patients with mild pain (visual analog scale score from 3-4 to 1) and in 75% of the patients with moderate pain (visual analog scale score from 5-6 to 2). After the second cycle, we recorded an improvement of pain and disability in all patients with moderate pain (P .01), but in 26% of patients with severe pain we did not record any improvement in disability (P .05). In conclusion we evaluated the role of um-PEA in patients with lumbar radiculopathy with a long-term follow-up (24 months) and put in evidence the effectiveness and the safety of this formulation in patients with mild and moderate pain.

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.

Objective. The aim of this study was to establish the prevalence of hemodialysis headache in a population of Calabrian subjects, in Italy. Methods. We observed a sample of hemodialysis subjects, studied at the University Hospital of Catanzaro and the Hospital of Melito PS, Reggio Calabria. The patients were investigated for the search for hemodialysis headache. The inclusion criteria of the subjects in the study were respected, such as the characteristics of the headache and the close relationship with dialysis. Results. The results showed a percentage of hemodialysis headache around 5% of cases. The percentage we found was very low compared with some literature data revealing percentages up to 70% of cases. Conclusions. This discrepancy of data is unclear, the results we obtained are in line with few cases of literature. However, our results pose important reflections on the actual prevalence of hemodialysis headache.

Background: Neck-tongue syndrome is a disorder causing unilateral neck pain, accompanied by simultaneous ipsilateral numbness of the tongue. It is explicable by compression of the second cervical root in the atlantoaxial space on sharp rotation of the neck. It may be secondary, idiopathic, familial, more frequent in females, in young people and the pain lasts from a few seconds to a few minutes. Treatment is symptomatic but also prophylactic, benefit is made by physiotherapy treatment. International Headache Society (IHS) places it between “Painful lesions of the cranial nerves and other facial pain”, describing as sudden onset of pain in the occiput or upper neck associated with abnormal sensation in the same side of the tongue. Methods: A 42-year-old female, who a month after reported a whiplash injury, following a car accident, manifested the symptoms of neck-tongue syndrome. The rotational movements of the head to the right side provoked intense pain in the neck and along the right half of the tongue. The pain also appeared spontaneously, duration varied from a few seconds to few minutes, associated with burning, frequency of about two episodes per day. Radiography and cervical spine MRI showed signs of spondylosis. Results: Topiramate combined with non-steroidal anti-inflammatory drugs, improved pain both in the neck and the tongue, reducing the episodes in frequency and intensity. Conclusions: Neck-tongue syndrome is a rare disorder, which manifests with pain in the neck and pain associated with burning of half of the tongue, by unknown etiology. Secondary forms following whiplash injury have not been described, Treatment of these secondary forms concerns use of symptomatic drugs for pain, buth also anticonvulsants as prophylaxis. Keywords: Neck-tongue syndrome, Headache, Cervical whiplash

Cerebral cavernous angioma or cavernoma is a benign vascular malformation, usually asymptomatic. It is infrequent and often its discovery is incidental, a so-called incidentaloma. However, these lesions can be symptomatic, causing headaches, epilepsy, cerebral hemorrhage and other neurological signs depending on the brain area involved. Frontal localization is responsible for psychiatric disorders, particularly the prefrontal region, leading to prefrontal syndrome, a condition common in all frontal lobe tumors. Psychopathological syndrome can be depression-type, pseudodepression syndrome or maniac-type, pseudomaniac syndrome. Surgical treatment of lesions like this may not always be possible due to their location in eloquent areas. In this study, we describe an unusual association of migraine-like headache, epilepsy and frontal lobe pseudodepression late-onset syndrome in the same patient. We have considered this case interesting mainly for the rarity of both a headache with migraine features and for the late onset of pseudodepression syndrome. Pathophysiology underlying migraine-like headache and that concerning the late-onset pseudodepression frontal lobe syndrome seems to be unclear. This case leads to further hypotheses about the mechanisms responsible for headache syndromes and psychopathological disorders, in the specific case when caused by a cerebral frontal lobe lesion.

Nummular headache is a very rare form of epilepsy.The main characteristics are the intensity of pain and rarity. The case we have described is the third one discovered in Italy, while only 200 cases have been reported worldwide. The response to drugs is not always effective. We treated the patient with a combination of palmitoylethanolamide and topiramate, the treatment was successful and the patient had a significant improvement in headache. Today, after 3 years we report the case, we are describing the course of headache. Three years later, the patient is almost free from painful attacks and shows a qualitatively better life. In addition, the improvement of headache has allowed the reduction of the topiramate, to avoid the appearance of adverse effects.

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.

MicroRNAs (miRs) have emerged as biomarkers of migraine disease in both adults and children. In this study we evaluated the expression of hsa-miR-34a-5p and hsa-miR-375 in serum and saliva of young subjects (age 11 &plusmn, 3.467 years) with migraine without aura (MWA), while some underwent pharmacological treatment, and healthy young subjects were used as controls. miRs were determined using the qRT-PCR method, and gene targets of hsa-miR-34a-5p and hsa-miR-375 linked to pain-migraine were found by in silico analysis. qRT-PCR revealed comparable levels of hsa-miRs in both blood and saliva. Higher expression of hsa-miR-34a-5p and hsa-miR-375 was detected in saliva of untreated MWAs compared to healthy subjects (hsa-miR-34a-5p: p &lt, 0.05, hsa-miR-375 p &lt, 0.01). Furthermore, in MWA treated subjects, a significant decrease of hsa-miR-34a-5p and of hsa-miR-375 was documented in saliva and blood compared to MWA untreated ones. Altogether, these findings suggested thathsa-miR-34a-5p and hsa-miR-375 are expressed equally in blood and saliva and that they could be a useful biomarker of disease and of drug efficacy in patients with MWA.

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.

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.

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.

Epilepsy in the elderly is a very debated case because much depends on the causes and associated pathologies. In particular, in the presence of comorbidity it is often difficult to find an effective and safe antiepileptic therapy that does not interfere with other drugs and therefore must be personalized. New-onset epilepsy in the elderly is caused by two types of cerebral lesions: The first concerns progressive, evolutive lesions, on which one can intervene, such as tumors or cerebrovascular pathologies, often acute.

Background Von Hippel-Lindau (VHL) disease is an autosomal dominant condition characterized by formation of multiple benign and malignant tumors. In this disease supratentorial lesions are rare and no falcine meningioma has been previously reported. Differential diagnosis is very difficult and the histopathological examination is the definitive method for diagnosis. Case description A patient with VHL underwent a suboccipital craniotomy for removal of cerebellar hemangioblastoma and after 2 years magnetic resonance imaging (MRI) showed an iperintense solid mass located at posterior part of the falx. Histological diagnosis revealed meningioma. Conclusion The only case in the literature of falcine meningioma in a patient with Von Hippel-Lindau disease, discovered during radiological follow-up, is described and a surgical management is proposed.