Selective cranial multineuritis in severe COVID-19 pneumonia: two cases and literature review.

OBJECTIVE: To report two cases of cranial multineuritis after severe acute respiratory syndrome caused by coronavirus-2. METHODS: Patients' data were obtained from medical records of the clinical chart of dell'Angelo Hospital, Venice, Italy. RESULTS: The first patient is a 42-year-old male patient who developed, 10 days after the resolution of coronavirus-2 pneumonia and intensive care unit hospitalization with hyperactive delirium, a cranial multineuritis with asymmetric distribution (bilateral hypoglossus involvement and right Claude Bernard Horner syndrome). No albumin-cytologic dissociation was found in cerebrospinal fluid; severe bilateral denervation was detected in hypoglossus nerve, with normal EMG of other cranial muscles, blink reflex, and cerebral magnetic resonance with gadolinium. He presented a striking improvement after intravenous human immunoglobulin therapy. The second case is a 67-year-old male patient who developed a cranial neuritis (left hypoglossus paresis), with dyslalia and deglutition difficulties. He had cerebrospinal fluid abnormalities (albumin-cytologic dissociation), no involvement of ninth and 10th cranial nerves, diffuse hyporeflexia, and brachial diparesis. DISCUSSION: Cranial neuritis is a possible neurological manifestation of coronavirus-2 pneumonia. Etiology is not clear: it is possible a direct injury of the nervous structures by the virus through olfactory nasopharyngeal terminations. However, the presence of albumin-cytological dissociation in one patient, the sparing of the sense of smell, and the response to human immunoglobulin therapy suggests an immune-mediated genesis of the disorder.

Emerging issues on selection criteria of levodopa carbidopa infusion therapy: considerations on outcome of 28 consecutive patients.

Many studies confirmed the efficacy and safety of continuous infusion of intrajejunal levodopa/carbidopa gel (CIILG) for advanced Parkinson's disease (PD). Although this treatment is widely used, definite inclusion/exclusion criteria do not exist. In this prospective open-label study, we evaluated the long-term outcome in 28 consecutive patients and sought to detect any predictive factor to identify the best candidates for CIILG therapy. The assessment was carried out routinely at baseline, after 6 months and every year with UPDRS III-IV, FOG Questionnaire, non-motor symptoms scale, PD questionnaire (PDQ-8), cognitive and psychiatric status evaluation (MMSE, FAB, NPI) and caregiver's quality of life. 17/28 patients reached the 24-month follow-up. A statistically significant beneficial effect was shown on motor complications in short- and long-term follow-up, also on axial symptoms like gait disturbances. A concomitant improvement in PDQ8 score was observed, with a parallel mild amelioration, but not significant, on Caregivers QoL. When classified according to their outcome on QoL, the only predictive positive factor was less severe at Neuropsychiatric Inventory (NPI) score at baseline. Considering the improvement in motor scores (duration of "off" period), the more advanced age was associated with a poorer outcome. Our results confirmed a sustained efficacy and safety in long-term follow-up and suggest that younger age at operation and absence or mild presence of psychiatric/behavioural symptoms could be considered valid predicting factors in selecting the best candidates for this efficacious therapy.

Five-year follow-up of 10 patients treated with globus pallidus internus deep brain stimulation for segmental or multisegmental dystonia.

INTRODUCTION: Globus pallidus internus (GPi) deep brain stimulation (DBS) represents a validated, effective, and safe treatment for patients affected by generalized dystonia resistant to conservative treatment. Segmental and multisegmental dystonia have more recently been proposed as further indications for GPi DBS despite the lack of long-term homogenous follow-up. Here we present an original and detailed long-term follow-up (5 years) of a homogeneous population of 11 patients affected by segmental or multisegmental dystonia. MATERIALS AND METHODS: Ten patients underwent bilateral GPi DBS electrode implantations under a Leksell stereotactic guide, with intraoperative neurophysiological monitoring. The follow-ups at 1, 3 and 5 years were collected using video-BFMDRS for motor and disability scores. The statistical analysis of the results is provided. RESULTS: We reported a statistically significant improvement in motor and disability overall scores until 5 years after treatment. At the last follow-up, even the single motor subitems were statistically improved. DISCUSSION: We observed a continuous and statistically significant improvement in all of the motor subitems and in the overall disability score until the 3-year follow-up. These results did not improve any further but they appeared steady at the last follow-up. We also report a significant improvement in the cranial-cervical subitems. CONCLUSIONS: GPi DBS should definitely be considered a safe and effective treatment also for segmental and multisegmental dystonia even in cases of relevant or prevalent cranial-cervical involvement.

Spinal anesthesia and minimal invasive laminotomy for paddle electrode placement in spinal cord stimulation: technical report and clinical results at long-term followup.

OBJECT: We arranged a mini-invasive surgical approach for implantation of paddle electrodes for SCS under spinal anesthesia obtaining the best paddle electrode placement and minimizing patients' discomfort. We describe our technique supported by neurophysiological intraoperative monitoring and clinical results. METHODS: 16 patients, affected by neuropathic pain underwent the implantation of paddle electrodes for spinal cord stimulation in lateral decubitus under spinal anesthesia. The paddle was introduced after flavectomy and each patient confirmed the correct distribution of paresthesias induced by intraoperative test stimulation. VAS and patients' satisfaction rate were recorded during the followup and compared to preoperative values. RESULTS: No patients reported discomfort during the procedure. In all cases, paresthesias coverage of the total painful region was achieved, allowing the best final electrode positioning. At the last followup (mean 36.7 months), 87.5% of the implanted patients had a good rate of satisfaction with a mean VAS score improvement of 70.5%. CONCLUSIONS: Spinal cord stimulation under spinal anesthesia allows an optimal positioning of the paddle electrodes without any discomfort for patients or neurosurgeons. The best intraoperative positioning allows a better postoperative control of pain, avoiding the risk of blind placements of the paddle or further surgery for their replacement.

Awake surgery in low-grade gliomas harboring eloquent areas: 3-year mean follow-up.

Low-grade gliomas are slow-growing tumors invading eloquent areas and white matter pathways. For many decades these tumors were considered inoperable because of their high tropism for eloquent areas. However, the young age of the patients and the inescapable anaplastic transformation have recently suggested more aggressive treatments. We analyzed the neurological and neuro-oncological outcome of 12 patients who underwent surgery fully awake for the resection of LGG, harboring eloquent areas. 10 right- and 2 left-handed patients underwent pre-operative assessment: Karnofsky Performance Status, Edinburgh Handedness Inventory Score; neuropsychological and neurophysiological evaluations, according to the tumor location. During surgery we performed: sensory-motor-evoked potentials, continuous electro-corticography and bipolar/monopolar cortico-subcortical mapping during neuropsychological tests. The resection rate was calculated with neuro-imaging elaboration software. No permanent post-operative deficits were reported; 2 patients improved after surgery. No impairment of cognitive functions was reported. The KPS improved in 8 patients and was steady in the others. The mean resection rate was 78.3%. The resection allowed the control of pre-operative seizures without increasing the drug intake. Awake surgery allowed a good resection rate despite the eloquent location of the tumors, without post-operative deficit. The neuropsychological outcome was unchanged after surgery. The resection seems to improve seizure control. All the patients came back to normal life and work. In conclusion, awake surgery is reliable and feasible in removal of LGG, even if invading the main eloquent areas and networks. All the patients experienced a normal life after surgery, without permanent deficits.

Recommendations of the International Society of Intraoperative Neurophysiology for intraoperative somatosensory evoked potentials.

Intraoperative somatosensory evoked potentials (SEPs) provide dorsal somatosensory system functional and localizing information, and complement motor evoked potentials. Correct application and interpretation require in-depth knowledge of relevant anatomy, electrophysiology, and techniques. It is advisable to facilitate cortical SEPs with total intravenous propofol-opioid or similarly favorable anesthesia. Moreover, SEP optimization is recommended to enhance surgical feedback speed and accuracy by maximizing signal-to-noise ratio (SNR); it consists of selecting highest-SNR peripheral and cortical derivations while omitting low-SNR channels. Confounding factors causing non-surgical SEP reduction should be excluded before issuing a warning. It is advisable to facilitate their identification with peripheral SEP controls and cortical SEP systemic controls whenever possible. Warning criteria should adjust for baseline drift and reproducibility. The recommended adaptive warning criterion is visually obvious amplitude reduction from recent pre-change values and clearly exceeding trial-to-trial variability, particularly when abrupt and focal. Acquisition and interpretation should be done by qualified technical and professional level personnel. Indications for SEP monitoring include intracranial, posterior fossa, and spinal neurosurgery, as well as orthopedic spine, cerebrovascular, and descending aortic surgery. Indications for SEP mapping include sensorimotor cortex and dorsal column midline identification. Future advances could modify current recommendations.

Clinical use of non-A botulinum toxins: botulinum toxin type C and botulinum toxin type F.

Botulinum neurotoxin (BoNT) serotype A is commonly used in the treatment of focal dystonia, but some patients are primarily or become secondarily resistant to it. Consequently, other serotypes have to be used when immuno-resistance is proven. In the literature, patients with focal dystonia have been treated with BoNT serotype F with clinical benefit but with short lasting effects. Recently, BoNT serotype C has been used with positive clinical outcome. An update on the clinical use of BoNT serotype F and BoNT serotype C is provided.

Epidemiological study of myasthenia gravis in the province of Ferrara, Italy.

The only prevalence rate of myasthenia gravis (MG) so far estimated in Italy by an epidemiological study carried out in Pavia, North Italy, indicates a prevalence quite similar to that observed in other countries. The purpose of the survey was to verify the frequency of the disease in a geographically well-defined and previously surveyed community. On the basis of 39 cases, on 31 December 1987 the prevalence per million was 105.3 (102.3 if standardized for the Italian population). This is the highest prevalence figure yet found, indicating a value similar to that established in Northern Europe. According to Kurtzke this high prevalence rate reflects the high standard of the local public health service, which permitted a more intensive search for affected subjects.

Recovery cycle of the masseter inhibitory reflex after magnetic stimulation in normal subjects.

OBJECTIVE: To evaluate the differences in the recovery cycle of the masseter inhibitory reflex (MIR) obtained with electrical and magnetic stimulation. METHODS: In 31 healthy subjects we studied the MIR evoked by electrical or magnetic stimulation of the mental territory and the recovery cycle of this reflex with the paired stimuli technique at different interstimulus intervals (ISI), between 100 and 600 ms. RESULTS: Latency and area of the early and late silent periods (SPs) of the MIR were similar after electrical and magnetic stimulation. The recovery cycle of the test late SP was similar with the two kinds of stimulation, except for short ISIs. The main difference between the two kinds of stimulation was in the painful quality of the stimulus: the magnetic stimuli were always below pain threshold. CONCLUSIONS: As with electrical stimulation, it is possible to obtain a MIR with magnetic peripheral stimulation. The magnetic paired stimuli are equally effective in the evaluation of the recovery cycle of the MIR. The results demonstrate that magnetic stimulation is a useful tool in the evaluation of excitability of the trigeminal motoneuronal system, with little discomfort for the patient. They also confirm the unlikelihood of nociceptive afferences involvement.

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.

Explosive-aggressive behavior related to bilateral subthalamic stimulation.

We describe a patient with Parkinson's Disease who underwent bilateral subthalamic nucleus deep brain stimulation and later presented with episodes of aggressive behavior disorder with disturbed impulse control and an inability to control anger likely related to the deep brain stimulation "switch-on stimulation". We hypothesize that increasing voltage intensity could influence neighboring passing fibers coming from basal limbic system that are involved in the regulation of affect and emotional behavior. We suggest investigating these neuropsychological disturbances considering their influence on quality of life after surgery.

Neurophysiological evaluation of the muscular hypotrophy after immobilization.

Muscular hypotrophy due to arm or leg immobilization (MH) in absence of neuromuscular pathologies was tested by EMG spectral analysis, in order to identify a possible neurophysiological method able to analyze this kind of particular clinical picture. Two different groups of patients were tested. In group 1 the patients were suffering from vastus medialis muscle MH due to meniscus surgery, in group 2 the patients were suffering from biceps brachii muscle MH after humerus fracture. A significant difference between normal and pathological muscles was found and the methods may be useful in the neurophysiological evaluation of MH.

The relationship between cerebral vascular disease and parkinsonism: The VADO study.

BACKGROUND: The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. METHODS: We recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy. RESULTS: We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. CONCLUSIONS: Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.

Effect of slow rTMS of motor cortex on the excitability of the blink reflex: a study in healthy humans.

OBJECTIVE: To evaluate the after-effects of low frequency, sub-threshold repetitive Transcranial Magnetic Stimulation (rTMS) of primary motor cortex, on the excitability of Blink Reflex (BR) in healthy subjects. METHODS: The BR recovery cycle was carried out in 10 healthy volunteers in basal conditions, immediately after rTMS (30s), 15 and 60min later. A paired electric supraorbital stimulus paradigm with inter-stimulus intervals (ISI) of 100-600-1000-1500ms was used. The "real" rTMS consisted of a 200 stimuli long train delivered at 1Hz and intensity 80% of rest Motor Threshold of the FDI muscle, using a focal coil applied over the primary motor cortex region. The basal BR recovery cycle was also compared with that obtained after a "sham" rTMS. RESULTS: The recovery of the R2 component of the BR was significantly suppressed 30s after rTMS. This effect was also observed at 15min, though of lower magnitude and only at long ISIs (1000-1500ms). No significant effect on R2 recovery was observed 60min after real rTMS as well as after sham rTMS. CONCLUSIONS: rTMS of motor cortex modulates the excitability of BR through its action on cortical excitability and on the cortical facilitatory drive to the brainstem reflex pathways. SIGNIFICANCE: Slow (1Hz), sub-threshold rTMS of motor cortex determines a long-lasting reduction of excitability of BR.

Hypokaliemic rhabdomyolysis associated with liquorice ingestion: report of an atypical case.

We here present an unusual case of hypokaliemic rhabdomyolysis, characterised by a sthenic deficit exclusively involving the distal muscles of the upper limbs and secondary to chronic glycyrrhizic acid intoxication, and by the absence of even ictal arterial hypertension. We discuss the etiopathogenetic bases and the risks related to the development of this secondary hypokaliemic syndrome, also in relation to other concomitant risk factors such as prolonged physical exercise and exposure to low temperatures.

Electrical field stimulation of isolated primate sweat glands.

An in vitro method is described for inducing secretion in isolated monkey eccrine sweat glands by means of electrical field stimulation (EFS). Ultrastructural analyses of these glands revealed unmyelinated nerve fibres surrounding the secretory coils. Numerous small clear vesicles, characteristic of cholinergic nerve terminals, were observed, along with a few which were large and dense-cored. EFS elicited an immediate secretory response which ceased abruptly upon termination of the current. The response was inhibited in a dose-dependent manner by atropine (IC50 1.5 X 10(-9) mol/l). Although most glands were completely inhibited by atropine, a minor atropine insensitive component was operative in some preparations. Physostigmine (10(-6) mol/l) potentiated the response to subthreshold EFS. Lidocaine (3 X 10(-4) mol/l) completely and reversibly blocked EFS but had no effect on methacholine (10(-6) mol/l) induced secretion. These results confirm that eccrine sweat gland activation is predominantly via cholinergic pathways and that EFS of isolated glands may be a useful model to study the control of secretory function in normal and diseased states.

Cation distributions across the larval and pupal midgut of the lepidopteran, Hyalophora cecropia, in vivo.

1. The levels of potassium, sodium, magnesium and calcium in leaves, midgut contents, midgut tissue, and blood were analysed in seven developmental stages between feeding, fourth-instar larvae and new pupae of the Cecropia silkworm. 2. Three dramatic changes in cation levels were found: the K level in the contents drops from 284 /+- 51 mEquiv./1 tissue water in the fifth-instar larva to 51 +/- 6 mEquiv./1 in the new pupa; the Mg level in the midgut tissue increases from 28 +/- 3 mEquiv./1 at the time of gut evacuation to 1093 +/- 104 mEquiv./1 in the new pupa; and the Ca level in the contents drops temporarily from 56 +/- 12 mEquiv./1 in the feeding fourth instar larva to 17 +/- 5 mEquiv./1 in the new fifth instar larva. The Na level was nerve higher than 2.8 +/- 0.5 mEquiv./1. 3. The relative levels of the four cations were different for each tissue studied, but each tissue maintained the same relative levels during the developmental stages studied. The sequences are: leaf, Ca greater than K GREATEr than Mg greater than Na; midgut contents, K greater than Ca greater than Mg greater than Na; midgut tissue, K GREATEr than Mg greater than Ca greater than Na; and blood, Mg greater than K greater than Ca greater than Na. 4. There were three large concentration gradients across the midgut; the K level in the midgut contents is approximately 10 times the level in blood; the Mg level in contents is one-half to one-sixth the level in blood; and the Ca level in contents is 3-4 times the level in blood. The K gradient and the Ca gradient are opposed and the Mg gradient is favoured by the electrical gradient across the larval midgut, the contents being 100 mV positive with respect to the blood. The K gradient and the electrical gradient are not present across the pupal midgut while the Mg gradient and the Ca gradient persist. 5. The K gradient is presumably maintained by the midgut K pump, the Mg gradient is aided by the midgut Mg pump, and the Ca gradient suggests that the midgut may possess a Ca pump.