A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details.

BACKGROUND AND PURPOSE: We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. METHODS: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. RESULTS: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barré syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. CONCLUSIONS: This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.

Time trends, frequency, characteristics and prognosis of short-duration transient global amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. METHODS: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977-1987 versus Oxford Vascular Study (OXVASC) 2002-2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002-2018]. We compared the risk factors, clinical features and long-term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. RESULTS: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long-term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. CONCLUSIONS: Short-duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long-term prognosis of short-duration TGA did not differ from more typical episodes lasting ≥ 1 h.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

Substantia nigra hyperechogenicity in essential tremor and Parkinson's disease: a longitudinal study.

BACKGROUND AND PURPOSE: Essential tremor (ET) and Parkinson's disease (PD) sometimes overlap in their clinical expression with ET preceding PD onset, often leading to misdiagnosis. Transcranial sonography (TCS) has been shown to be a valid and non-invasive diagnostic tool to identify early idiopathic PD and to differentiate it from ET. The purpose of this study was to investigate the relevance of substantia nigra hyperechogenicity in patients with ET. METHODS: A total of 138 patients (79 with PD, 59 with ET) and 50 matched controls underwent TCS examination at baseline. All patients were followed in a 3-year longitudinal assessment. RESULTS: A total of 10 subjects were excluded from the analysis due to the bilateral absence of a temporal acoustic window. During the follow-up period, 11 of the patients with ET developed new-onset parkinsonian features, without fulfilling criteria for PD diagnosis (ET+). Nine patients developed clinical features meeting diagnostic criteria for probable PD (ET-PD). Patients with ET- did not develop parkinsonian features. For each group, the maximum size of the substantia nigra hyperechogenicity was as follows: 5.62 ± 5.40 mm2 in the control group, 19.02 ± 14.27 mm2 in patients with PD, 9.15 ± 11.26 mm2 in patients with ET-, 20.05 ± 13.78 mm2 in patients with ET+ and 20.13 ± 13.51 mm2 in patients with ET-PD. ET-PD maximum values were significantly different from controls. Maximum values in patients with ET+ were different from both controls and patients with ET-. CONCLUSION: Substantia nigra hyperechogenicity in ET seems to represent a risk marker for developing early parkinsonian symptoms or signs in the 3 years following TCS assessment.

Neuropsychiatric adverse events of antiepileptic drugs in brain tumour-related epilepsy: an Italian multicentre prospective observational study.

BACKGROUND AND PURPOSE: We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). METHODS: This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. RESULTS: Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. CONCLUSIONS: Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Prognostic factors in children with PRES and hematologic diseases.

OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by focal neurological signs, headache, confusion, and seizure, associated with transitory lesions in the posterior areas of the brain detectable with neuroimaging. Among children, one of the most common causes of PRES is cancer. MATERIALS AND METHODS: In this review, we present the cases of 5 children developing PRES after stem cell transplantation for hematological disease and review all the cases reported in English literature to investigate outcomes and associated risk factors. RESULTS: One hundred and eleven cases were reported. Hypertension was very frequent (80%). Clinical features included seizures (80.1%), headache (44.1%), visual disturbance (26.1%), and mental change (48.6%). EEG was abnormal in 27 of 32 patients. MRI revealed characteristic lesions in all patients even in early stages. Abnormal MRI findings in late stages were associated with neurological sequelae. Nineteen patients died (17.1%) of which 2 of PRES. Among alive patients, 17 had neurological sequelae. Four cases of PRES relapse were described. CONCLUSIONS: Thus, all transplant recipients with symptoms consistent with PRES should be promptly recognized to avoid long-term complications or even death.

Ear acupuncture and fMRI: a pilot study for assessing the specificity of auricular points.

In recent years research explored different acupuncture stimulation techniques but interest has focused primarily on somatic acupuncture and on a limited number of acupoints. As regards ear Acupuncture (EA) there is still some criticism about the clinical specificity of auricular points/areas representing organs or structures of the body. The aim of this study was to verify through (Functional magnetic resonance imaging) fMRI the hypothesis of EA point specificity using two auricular points having different topographical locations and clinical significance. Six healthy volunteers underwent two experimental fMRI sessions: the first was dedicated to the stimulation of Thumb Auricular Acupoint (TAA) and the second to the stimulation of Brain Stem Auricular Acupoint (BSAA). The stimulation of the needle placed in the TAA of the left ear produced an increase in activation bilaterally in the parietal operculum, region of the secondary somatosensory area SII. Stimulation of the needle placed in the BSAA of the left ear showed a pattern that largely overlapped regions belonging to the pain matrix, as shown to be involved in previous somatic acupuncture studies but with local differences in the left amygdala, anterior cingulate cortex, and cerebellum. The differences in activation patterns between TAA and BSAA stimulation support the specificity of the two acupoints. Moreover, the peculiarity of the regions involved in BSAA stimulation compared to those involved in the pain matrix, is in accordance with the therapeutic indications of this acupoint that include head pain, dizziness and vertigo. Our results provide preliminary evidence on the specificity of two auricular acupoints; further research is warranted by means of fMRI both in healthy volunteers and in patients carrying neurological/psychiatric syndromes.

HERSCHEL/SCORE, imaging the solar corona in visible and EUV light: CCD camera characterization.

The HERSCHEL (helium resonant scattering in the corona and heliosphere) experiment is a rocket mission that was successfully launched last September from White Sands Missile Range, New Mexico, USA. HERSCHEL was conceived to investigate the solar corona in the extreme UV (EUV) and in the visible broadband polarized brightness and provided, for the first time, a global map of helium in the solar environment. The HERSCHEL payload consisted of a telescope, HERSCHEL EUV Imaging Telescope (HEIT), and two coronagraphs, HECOR (helium coronagraph) and SCORE (sounding coronagraph experiment). The SCORE instrument was designed and developed mainly by Italian research institutes and it is an imaging coronagraph to observe the solar corona from 1.4 to 4 solar radii. SCORE has two detectors for the EUV lines at 121.6 nm (HI) and 30.4 nm (HeII) and the visible broadband polarized brightness. The SCORE UV detector is an intensified CCD with a microchannel plate coupled to a CCD through a fiber-optic bundle. The SCORE visible light detector is a frame-transfer CCD coupled to a polarimeter based on a liquid crystal variable retarder plate. The SCORE coronagraph is described together with the performances of the cameras for imaging the solar corona.

No enhancement of fusion probability by the neutron halo of 6He.

Quantum tunnelling through a potential barrier (such as occurs in nuclear fusion) is very sensitive to the detailed structure of the system and its intrinsic degrees of freedom. A strong increase of the fusion probability has been observed for heavy deformed nuclei. In light exotic nuclei such as 6He, 11Li and 11Be (termed 'halo' nuclei), the neutron matter extends much further than the usual nuclear interaction scale. However, understanding the effect of the neutron halo on fusion has been controversial--it could induce a large enhancement of fusion, but alternatively the weak binding energy of the nuclei could inhibit the process. Other reaction channels known as direct processes (usually negligible for ordinary nuclei) are also important: for example, a fragment of the halo nucleus could transfer to the target nucleus through a diminished potential barrier. Here we study the reactions of the halo nucleus 6He with a 238U target, at energies near the fusion barrier. Most of these reactions lead to fission of the system, which we use as an experimental signature to identify the contribution of the fusion and transfer channels to the total cross-section. At energies below the fusion barrier, we find no evidence for a substantial enhancement of fusion. Rather, the (large) fission yield is due to a two-neutron transfer reaction, with other direct processes possibly also involved.

Alopecia areata and homolateral headache due to an impacted superior wisdom tooth.

A case of alopecia areata and homolateral headache due to an impacted superior wisdom tooth is reported. After the extraction, the headache disappeared, hair regrew in the alopecic area and in 4 months completely covered the whole area.

International research project to devise a protocol to test the effectiveness of acupuncture on painful shoulder.

OBJECTIVES: To describe in detail the questions and deliberations leading to the development of a methodologically rigorous protocol to test the effectiveness of acupuncture on painful shoulder. DESIGN: Randomized controlled trial using three groups, including one control group. SETTINGS/LOCATION: A hospital in the north of Italy treating at least 8-10 painful shoulders a day, with physician/acupuncturists, physiotherapists, and assessors available to participate in the study. SUBJECTS: Sixty patients with monolateral painful shoulder. A list of exclusion criteria is given. INTERVENTIONS: Acupuncture + mobilization; mobilization alone (control); ear acupuncture + mobilization. OUTCOME MEASURES: Severity of pain, scored on a visual analogue scale (VAS) and on the McGill Pain Questionnaire and restriction of range of motion (ROM) of the shoulder joint. Voluntary use of pain medication, Tenoxicam 20 mg, was added to the protocol. RESULTS: The research team developed a protocol and methodology that avoids the common flaws and difficulties of previous clinical trials on acupuncture. CONCLUSIONS: Physicians and acupuncture specialists will benefit from the advice and support of a project group consisting of experienced clinicians, researchers, and statisticians when designing and preparing clinical trials on acupuncture and other complementary and alternative therapies.

[Preliminary considerations on changes in pigmentation, structure and vascularization of the outer ear in relation to chronic organic or functional disease]. / Considerazioni preliminari su alterazioni di pigmentazione, di struttura, di vascolarizzazione del padiglione auricolare, in relazione ad una patologia cronica organica o funzionale.

With this preliminary note the Authors propose a study of morphological changes and discolorations of the skin of the auricle in correlation with a chronic pathology. They present an extensive report of 13 patients with a long-standing symptomatology between 3 and 20 years. Time factor and the laterality problems are discussed.

[Electromyographic changes in bruxism after auricular stimulation. A randomized controlled clinical trial]. / Variazioni elettromiografiche nel bruxismo dopo stimolazione auricolare. Uno studio clinico controllato e randomizzato.

AIM: The aim of this study was to verify in bruxism patients the possible efficacy of auricular stimulation in reducing the hypertonicity of some masticatory muscles. METHODS: Forty-three bruxism patients were randomly allocated to 3 groups: acupuncture, needle contact for 10 seconds, no treatment (control). Helkimo's clinical dysfunction index (CDI) and anamnestic dysfunction index (ADI) were used to assess the functional state of the masticatory system. The resting electrical activity of the anterior temporalis (AT), masseter (MM), digastric (DA) and sternocleidomastoid (SCM) muscles was measured, according to Jankelson, with surface electrodes at baseline, after stimulation and continually for 30 minutes (120 measurements in total). The electromyographical variations in the 3 groups were studied with t test for independent samples. RESULTS: Acupuncture and needle contact were superior to control in reducing the muscle hypertonicity of all muscles except SCM. In the comparison between acupuncture and needle contact the former showed better results only for the right TA and left DA (p = 0.000). CONCLUSION: In this study it was possible to measure the efficacy of the stimulation of only one point or area, which is an ideal model for research in acupuncture. The auricular area we chose for stimulation was never used before for the purpose of relaxing masticatory muscles. Acupuncture and needle contact for 10 seconds showed similar effects.

Ear acupuncture and psychosomatic medicine: right-left asymmetry of acupoints and lateral preferences--Part II.

A group of 50 patients with possible psychosomatic disorders was examined with five right-left preference tests: Oldfield's Handedness Inventory, and Coren and Porac's preference tests for hand, foot, eye and ear. The patients were sorted into "complete right" (consistent answers) and "incomplete right" (having answered "left" to at least one question) groups for each of these different tests. The sensitization of the left ear, particularly of the Sanjiao or Triple Heater area, is higher in the complete right than in the incomplete right group. The side to treat with Acupuncture is important for diagnosis and therapy.

Ear acupuncture in psychosomatic medicine: the importance of the Sanjiao (triple heater) area.

A group of 50 patients with possible psychosomatic disorders of the cardiovascular, respiratory and digestive systems were treated with Ear acupuncture. Together with a control group of 20 symptomless volunteers they received 4 weekly treatments and a final check of the therapy after 6 weeks. All subjects were examined with the MMPI test, Paykel's scale for stressful life events, and with the SRT scale (Symptom Rating Test) for measuring at each treatment the variations of anxiety, depression and somatisation levels. The results show a similar trend of response to Acupuncture in both groups, which was significantly more pronounced in the stress group for the reduction of the SRT score and the number of Ear acupuncture points. The outer ear was sensitized by stress response in certain recurrent areas, especially of the cavum conchae. The area with the highest relative density of Ear acupoints was the Sanjiao or Triple Heater area.

Diagonal ear-lobe crease: possible significance as cardio-vascular risk factor and its relationship to ear-acupuncture.

The diagonal ear-lobe crease, detectable especially after the age of 40, is still accepted as a sign of coronary heart disease risk. In the literature some authors report an association between anxiety and coronary heart disease. In our work a group of 143 patients with ear-lobe crease showed - in both sexes and in all examined decades (5th, 6th, 7th) - higher levels of anxiety than in the control group. The possible significance of the crease has been considered on the grounds of present knowledge of ear-acupuncture and the somatotopic mapping of CNS on the ear-lobe.

The therapeutic activity of sulphate-bicarbonate-calcium-magnesiac mineral water in the functional disorders of the biliary tract.

BACKGROUND AND AIM: Functional disorders of the biliary tract involve gallbladder and sphincter of Oddi and cause pain and/or digestive troubles. In this context, in addition to pharmacological treatments, an important role is played by the use of sodium-sulphate and sulphate-bicarbonate mineral waters that, because of their composition into ions macro and trace elements, can stimulate the release or modulate the activity of some neurohumoral regulators of the digestive process. We want to do a study on the effects of hydropinotherapy with a sulphate-bicarbonate-calcium-magnesium mineral water in patients suffering from pain and other symptoms caused by biliary dyskinesias, biliary sand (without gallstones), or following a cholecystectomy (post-cholecystectomy syndromes). MATERIALS AND METHODS: We enrolled 43 patients suffering from those affections; all the patients did two cycles in one year of hydropinotherapy with Acqua Santa at Italy's Chianciano Spa; 20 of these patients did a third cycle of hydropinotherapy in the second year of the study. At the end of the second and of the third cycle we compared the frequency of eleven main symptoms in both groups and we also performed an longitudinal-observational study on the frequency of those symptoms before the beginning of the first cycle of the therapy and at the end of the second and of the third cycle. Statistical analyses were based on the use of Pearson's χ2 test. RESULTS: The frequency of the symptoms observed at the end of second and third cicle of hydropinotherapy was significantly lower than that considered before starting therapy. The differences were statistically significant. CONCLUSIONS: The results of our research regarding the hydropinotherapy by sulphate-bicarbonate-calcium-magnesium mineral water show a significant improvement of symptoms in patients suffering from disturbances of biliary tract.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PURPOSE: The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. METHODS: VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. RESULTS: In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. CONCLUSIONS: Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk.