Camillo Negro (1861-1927) and his method for eliciting the extensor toe sign.

The "toe phenomenon", or extensor toe sign, is characterized by the extension (dorsiflexion) of the great toe elicited by plantar stimulation, and indicates pyramidal tract dysfunction. This phenomenon was first extensively described and studied by Joseph Jules François Félix Babinski (1857-1932), who introduced it in clinical practice. In 1912, the famous Italian neurologist Camillo Negro (1861-1927) proposed a new method of eliciting the extensor toe sign by inviting the patient, lying in bed in dorsal decubitus position, to raise the paretic limb with the leg extended on the thigh. This sign appeared during voluntary effort and could not be elicited by raising the unaffected lower limb. Negro was also the first to investigate the influence of cold upon the appearance of the "toe phenomenon" and to propose the use of (faradic) electrical stimulation to evoke it.

Vincenzo Neri (1880-1960) and his sign to detect leg weakness due to corticospinal tract injury.

The Italian neurologist Vincenzo Neri (1880-1960), a pupil of Joseph Babinski (1857-1932), greatly contributed to refining the semiotics of neurological examination and was a pioneer in medical cinematography. In 1909, Neri proposed a sign to diagnose leg paresis due to a pyramidal tract lesion. According to Neri, if a patient standing with the legs apart and the arms crossed on the chest bends the trunk of the pelvis, when the trunk has almost reached the horizontal line, the leg on the paralyzed side flexes, whereas the unaffected leg remains extended. This sign reflects a spinal hyperfunctioning emerging after a pyramidal lesion, and should be interpreted as a part of a triple flexion reflex. Beyond the acute stage, it could reflect an unusual pattern of flexor spasticity involving the lower limb due to corticospinal tract injury. The sign described by Neri retains its validity in identifying this organic leg weakness due to pyramidal lesions, particularly when it is mild or in its early stages.

Late epileptic seizures following cerebral venous thrombosis: a systematic review and meta-analysis.

BACKGROUND: Identifying late epileptic seizures (LS) following cerebral venous thrombosis (CVT) can be useful for prognosis and management. We systematically reviewed the literature to identify risk factors for LS due to CVT. METHODS: We systematically searched PubMed, Scholar, and Scopus databases (May 2021) to identify studies reporting data on prevalence and risk factors for CVT-LS. The methodological quality was assessed with the Ottawa-Newcastle Scale. The risk of developing CVT-LS was summarized in meta-analyses and expressed as odds ratio (OR) and corresponding 95% confidence intervals (CIs) using random-effects models. RESULTS: Out of the 332 records retrieved, four studies were eventually included with a total of 1309 patients with CVT and 142 (11%) with CVT-LS. The most relevant predictors of CVT-LS were symptomatic seizures (OR 5.66, 95% CI 3.83-8.35), stupor/coma (OR 6.81, 95% CI 1.18-39.20), focal neurologic signs (OR 6.81, 95% CI 1.18-39.2), hemorrhagic component (OR 3.52, 95% CI 2.45-5.06), and superior sagittal sinus involvement (OR 1.52, 95% CI 1.04-2.21). CONCLUSION: There are several risk factors for CVT-LS that should be considered in clinical practice. Further high-quality studies are warranted to develop predictive models for individualized risk stratification and prediction of CVT-LS.

Letter about "The song of Anorexia Nervosa: a specific evoked potential response to musical stimuli in affected participants" by Spalatro et al. (https://doi.org/10.1007/s40519-020-00898-4), published online: 05 May 2020.

In the article "The song of Anorexia Nervosa: a specific evoked potential response to musical stimuli in affected participants" by Spalatro et al., in the Methods section, a paragraph relating to N100 and P300 data acquisition is missing. Indeed, the stimulation paradigms and recording methods are not described. Furthermore, in the paragraph "N100 and P300 analysis", the related issues are missing. In the absence of the data mentioned, it is not possible to understand the results.

Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review.

BACKGROUND: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. MATERIAL AND METHODS: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. RESULTS: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. CONCLUSIONS: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Hypertension, seizures, and epilepsy: a review on pathophysiology and management.

BACKGROUND: Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy. METHODS: We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018. RESULTS: Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives. CONCLUSIONS: Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial.

OBJECTIVE: To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long-term health-related quality of life (HRQoL). METHODS: PuLsE (Open Prospective Randomized Long-term Effectiveness) was a prospective, randomized, parallel-group, open-label, and long-term effectiveness study (conducted at 28 sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n = 112) received VNS + BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory-89 total score; QOLIE-89). Secondary endpoints included changes in seizure frequency, responder rate (≥50% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES-D), Neurological Disorders Depression Inventory-Epilepsy scale (NDDI-E), Clinical Global Impression-Improvement scale (CGI-I), Adverse Event Profile (AEP), and antiepileptic drug (AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n = 362. Results for n = 96 who had baseline and at least one follow-up QOLIE-89 assessment (from months 3-12) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints. RESULTS: Significant between-group differences in favor of VNS + BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI-I score (respective p-values < 0.05, 0.03, and 0.01). More patients in the VNS + BMP group (43%) reported adverse events (AEs) versus BMP group (21%) (p = 0.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES-D, NDDI-E, AEP, and AED load. SIGNIFICANCE: VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

KCNK18 (TRESK) genetic variants in Italian patients with migraine.

OBJECTIVES: To evaluate the prevalence of KCNK18 gene mutations in a dataset of Italian migraineurs, with and without aura, and in healthy controls, and to investigate in silico the functional effects of the mutations. BACKGROUND: A role for the KCNK18 gene encoding for TRESK, a member of the family of potassium channel, has been recently suggested in migraine with aura. METHODS: We sequenced the KCNK18 gene in 425 migraineurs (255 with aura and 170 without aura) and 247 healthy controls. RESULTS: Five genetic variants (R10G, C110R, Y163Y, S231P, and F372L) were found in 13 (5.1%) out of 255 migraine with aura patients, and 6 variants (R10G, D46D, C110R, Y163Y, S178T, and S231P) were identified in 12 (7.1%) out of 170 migraine without aura patients. In 2.8% of controls, the R10G and L20V substitutions were found. In silico analysis suggested that C110R, S178T, S231P, and F372L mutations may have potential damaging effect on channel function, whereas the remaining mutations may have low damaging effect. CONCLUSIONS: Our study shows the presence of several KCNK18 gene mutations in both migraine with aura and migraine without aura. However, the precise role of this gene in migraine predisposition deserves further studies.

A functional polymorphism in the SCN1A gene does not influence antiepileptic drug responsiveness in Italian patients with focal epilepsy.

A splice site variation (c.603-91G>A or rs3812718) in the SCN1A gene has been claimed to influence efficacy and dose requirements of carbamazepine and phenytoin. We investigated the relationship between c.603-91G>A polymorphism and response to antiepileptic drugs (AEDs) in 482 patients with drug-resistant and 401 patients with drug-responsive focal epilepsy. Most commonly used AEDs were carbamazepine and oxcarbazepine. The distribution of c.603-91G>A genotypes was similar among drug-resistant and drug-responsive subjects, both in the entire population and in the groups treated with carbamazepine or oxcarbazepine. There was no association between the c.603-91G>A genotype and dosages of carbamazepine or oxcarbazepine. These findings rule out a major role of the SCN1A polymorphism as a determinant of AED response.

Nonconvulsive status epilepticus due to a de novo contralateral focus during tiagabine adjunctive therapy.

We describe a 30-year-old woman with an infantile-onset epilepsy due to a left temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE) during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de novo right temporal focus not previously evident. After the i.v. administration of 4 mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal EEG abnormalities reappeared. To our knowledge this is the first case of paradoxical seizure exacerbation associated with TGB therapy in which the clinical and EEG features are congruous with a new contralateral focus.