Angelo Franzini

Comparing neurostimulation technologies in refractory focal-onset epilepsy

For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5u2005years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy.

Management of Chronic Cluster Headache

Opinion statementPrimary cluster headache (CH) is an excruciatingly severe pain condition. Several pharmacologic agents are available to treat chronic CH, but few double-blind, randomized clinical trials have been conducted on these agents in recent years, and the quality of the evidence supporting their use is often low, particularly for preventive agents. We recommend sumatriptan or oxygen to abort ongoing headaches; the evidence available to support their use is good (Class I). Ergotamine also appears to be an effective abortive agent, on the basis of experience rather than trials. We consider verapamil and lithium to be first-line preventives for chronic CH, although the trial evidence is at best Class II. Steroids are clearly the most effective and quick-acting preventive agents for chronic CH, but long-term steroid use carries a risk of several severe adverse effects. We therefore recommend steroids only if verapamil, lithium, and other preventive agents are ineffective. In rare cases, patients experience multiple daily cluster headaches for years and are also refractory to all medications. These patients almost always develop severe adverse effects from chronic steroid use. Such patients should be considered for neurostimulation. Occipital nerve stimulation is the newest and least invasive neurostimulation technique and should be tried first; the evidence supporting its use is encouraging. Hypothalamic stimulation is more invasive and can be performed only in specialist neurosurgical centers. Published experience suggests that about 60% of patients with chronic CH obtain long-term benefit with hypothalamic stimulation.

Endoscopic laryngeal patterns in vagus nerve stimulation therapy for drug-resistant epilepsy

In 30xa0% of patients with epilepsy seizure control cannot be achieved with medications. When medical therapy is not effective, and epilepsy surgery cannot be performed, vagus nerve stimulator (VNS) implantation is a therapeutic option. Laryngeal patterns in vagus nerve stimulation have not been extensively studied yet. The objective was to evaluate laryngeal patterns in a cohort of patients affected by drug-resistant epilepsy after implantation and activation of a vagus nerve stimulation therapy device. 14 consecutive patients underwent a systematic otolaryngologic examination between 6xa0months and 5xa0years after implantation and activation of a vagus nerve stimulation therapy device. All patients underwent fiberoptic endoscopic evaluation, which was recorded on a portable device allowing a convenient slow-motion analysis of laryngeal patterns. All recordings were blindly evaluated by two of the authors. We observed three different laryngeal patterns. Four patients showed left vocal cord palsy at the baseline and during vagus nerve stimulation; seven showed left vocal cord palsy at the baseline and left vocal cord adduction during vagus nerve stimulation; and three patients showed a symmetric pattern at the baseline and constant left vocal cord adduction during vagus nerve stimulation. These laryngeal findings are here described for the first time in the literature and can be only partially explained by existing knowledge of laryngeal muscles and vagus nerve physiology. This might represent a new starting point for studies concerning laryngeal physiology and phonation, while the vagus nerve stimulation therapy could act as a new and ethical experimental model for human laryngeal physiology.

Drug-resistant primary headache patients undergoing surgical therapies: how should we assess outcomes?

The introduction of neurostimulation procedures for chronic drug-resistant primary headaches has offered new hope to patients, but has also introduced new problems. The methods to be used in assessing clinical outcomes and monitoring treatment efficacy need careful attention. The International Headache Society guidelines recommend that treatment efficacy should be monitored by getting patients to report the number of attacks per day, in a headache diary. The headache diary is a fundamental instrument for objectively assessing subjective pain in terms of headache frequency, intensity and duration and analgesic consumption. The huge discrepancy sometimes reported between patient satisfaction and headache improvement suggests that patient satisfaction should not be a primary efficacy endpoint, and more importantly should not be put forward as an argument in establishing the efficacy of highly experimental neurostimulation procedures.

A Singular Case of Neurosyphilis Manifesting Through a Meningovascular Chronic Inflammatory Process in Association with the Occurrence of Two Aneurysms Involving the Distal A2 Segment of Both Anterior Cerebral Arteries: A Case Report and Review of the Literature

BACKGROUNDnAlthough syphilis has become a rare disease in the Western world since the Second World War, it is believed to have infected 12 million people in 1999, with greater than 90% of cases occurring in the developing world. Moreover, since the year 2000, the rates of syphilis have been increasing in the United States, the United Kingdom, Australia, and Europe. Because of the mimic nature of the disease and the overall low rate of occurrence of its manifestations in advanced stages, a proper diagnosis may prove difficult.nnnCASE REPORTnWe report the case of a 41-year-old African man affected by neurosyphilis that manifested itself through a meningovascular chronic inflammatory process, with the peculiar feature of a bilateral aneurysm of probable mycotic origin involving the distal tract of A2 segment of both anterior cerebral arteries.nnnCONCLUSIONSnBecause of the mostly nonspecific nature of clinical manifestations of syphilis (particularly advanced syphilis) and its consequent tendency to masquerade as many other diseases, even a skilled physician may find its diagnosis quite challenging; thus, thorough clinical and radiologic investigations should be supported by serologic testing for syphilis in all cases of cognitive impairment. Mycotic intracranial aneurysms in association with neurosyphilis rarely are reported; however, they require early diagnosis and meticulous, individualized treatment. Because syphilis appears to be on the raise, further studies on the topic are warranted.

Shifting from constant-voltage to constant-current in Parkinson’s disease patients with chronic stimulation

The study aimed to evaluate safety and efficacy of shifting stimulation settings from constant-voltage (CV) to constant-current (CC) programming in patients with Parkinson’s disease (PD) and chronic subthalamic nucleus deep brain stimulation (STN DBS). Twenty PD patients with chronic STN DBS set in CV programming were shifted to CC and followed for 3xa0months; the other stimulation settings and the medication regimen remained unchanged. Side effects, motor, non-motor, executive functions, and impedance were assessed at baseline and during follow-up. No adverse events were observed at time of shifting or during CC stimulation. Motor and non-motor measures remained unchanged at follow-up despite impedance decreased. Compared to baseline, inhibition processes improved at follow-up. The shifting strategy was well tolerated and the clinical outcome was maintained with no need to adjust stimulation settings or medications notwithstanding a decrease of impedance. Improvement of inhibition processes is a finding which needed further investigation.

ONS and DBS for the Treatment of Chronic Cluster Headache

Research focus: Chronic cluster headache (CCH) is a pathological entity leading to a severe degree of disability. It is characterized by pain attacks occurring daily or spaced out by remission periods of <1 month, contrarily to the episodic form. When the condition results to be refractory to conservative treatments (both prophylactic and abortive treatments) and when such condition is present for at least 2 years, surgical treatment is suggested. Research methods: We here report our institutional experience with regard to both occipital nerve stimulation (ONS) and deep brain stimulation (DBS) for the treatment of the disease. Results/findings of the research: 15 out of 28 (65%) patients submitted to ONS had ≥50% reduction in 32 headache number per day and were considered responders; 12 out of 17 patients (70%) submitted to phyp DBS showed long-last improvement. Main conclusions and recommendations: Although no valid predictive factor is available at the moment, due to the lack of prospective and randomized studies, both procedures seem to constitute safe and valid treatments for such disabling condition.

Painful Rosacea as a Warning Sign of Intracranial Metastasis of Squamous Cell Carcinoma

The term “neurogenic rosacea” (NR) has been introduced recently to describe the association of rosacea with prominent symptoms related to neurological or psychiatric disorders, including depression, migraine, and complex regional pain syndrome. According to this rather loose definition, only 17 patients with NR have been fully described to date. NR is said to be mainly erythematous and characterized by flushing, erythema, facial edema, burning pain, and pruritus, whereas papules, pustules, and rhinophymatous changes would be less frequent in this setting, and should be suspected in any patients with rosacea where the predominant symptom is pain and/or burning sensation out of proportion to the flushing. These patients are generally unresponsive to treatment with metronidazole and tetracyclines. A neurologically focused approach by means of GABAergic agents or antidepressants has instead proved successful. Recently, the scope for association of rosacea with neurological disturbances has been extended: the incidence of rosacea in patients with facial dystonias such as benign essential blepharospasm and hemifacial spasm has been shown to be increased. Conversely, according to epidemiological data from Denmark, rosacea would be an independent risk factor for glioma, Parkinson disease, depression, and anxiety disorders, albeit with low adjusted incidence rate ratios below 2. Here we describe a case in which rosacea was a warning sign of an intracranial malignancy. In summer 2011, a 71-year-old man, treated for non-Hodgkin lymphoma (NHL) in 2008 and then in complete remission, started to complain of a progressive and severe left trigeminal pain and dysesthesia, involving all of the three branches, associated with left hemifacial flushes and persistent teleangiectatic erythema (erythrosis). A progressive and complete paralysis of the left extrinsic From the Department of Neurosurgery, Carlo Besta Neurological Institute, Milan, Italy (M. Rizzi, G. Messina, N. Castelli, and A. Franzini); Department of Neurosurgery, San Giovanni Battista Hospital, Turin and Resident Neurosurgery Program, University of Turin, Turin, Italy (F. Penner); Private practice, Dermatology & STD, Milan, Italy, formerly Consulting Dermatologist, Carlo Besta Neurological Institute, Milan, Italy (G.L. Capella).

Deep Brain Stimulation in Aggressive Behavior

Deep-brain stimulation (DBS) of the posterior hypothalamic region was originally introduced to treat trigeminal autonomic cephalalgias (TACs), which are thought to result from hyper-activation of the posterior hypothalamic region (pHr) occurring during bouts pain bouts in these pathologies. In fact, patients experiencing chronic luster headache attacks often exhibit aggressive bouts during such episodes. In the past, the posterior hypothalamic region (pHr) was used as a lesional target in patients with aggressive behavior , epilepsy and, mental retardation. Furthermore, disruptive behavior was found to be induced by acute electrical stimulation within the so-called “triangle of Sano” in a Parkinsonian patient. The known interconnections between the pHr, the amygdala, and the overall so-called “Papez circuit” may explain the role of the pHr in the development of disruptive behavior. The choice of targeting the pHr for this pathology is determined by the crucial role of pHr within the limbic circuits, which appear to be dysregulated according to several clinic and experimental data. We chose to use DBS to severely impaired patients affected by refractory aggressive behavior and mental retardation. The first surgery was performed in 2002. We here describe our technique and long-term follow-up in seven patients.