The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

Clinical characteristics and outcome of patients with autoimmune encephalitis: clues for paraneoplastic aetiology.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AE) represents a complex syndrome with diverse clinical manifestations and therapeutic outcomes. The aim of this study was to report the clinical characteristics and the long-term outcome of patients with paraneoplastic and idiopathic AE. METHODS: All patients with subacute encephalopathy admitted to the Neurology Department of our Institution from January 2012 to May 2019 were consecutively enrolled. Patients' serum and cerebrospinal fluid were tested for neural-specific autoantibodies by indirect immunofluorescence assays on mouse brain, rat neurons, cell-based assays and immunoblots. Outcome was assessed by the modified Rankin Scale score. RESULTS: From 107 adult patients with subacute encephalopathy, 50 patients were finally diagnosed with AE. Neural antibodies (Abs) were detected in 45/50 patients (90%). Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent (6/50, 12%) Ab specific to neural surface antigens detected in adults with AE. Paraneoplastic encephalitis was diagnosed in 16/50 patients (32%). The presence of bilateral temporal lobe lesions on magnetic resonance imaging and cerebrospinal fluid restricted oligoclonal bands was associated with a higher probability to detect cancer at the time of AE diagnosis. All patients with Abs to neural surface antigens had a good outcome at last follow-up. Severe disability at AE onset and the lack of long-term immunosuppression predicted a poor outcome. CONCLUSIONS: Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent Ab detected. Patients with bilateral temporal lobe lesions and oligoclonal bands have a higher probability to harbour an occult tumour. In these patients, a strict surveillance and monitoring for cancer detection is recommended.

Treatment-emergent central sleep apnoea after surgery for obstructive sleep apnoea.

Central sleep apnoea (CSA) is a lack of drive to breathe during sleep, which can occur in physiologic as well as in pathologic conditions. A particular type of CSA, defined treatment-emergent CSA (TECSA), may occur after the treatment of obstructive sleep apnoea syndrome (OSAS), either with CPAP or surgery. TECSA is transitory and seems to be related to the severity of OSAS. We describe a 51-year-old man affected by severe OSAS who developed severe, transient CSA immediately after upper airways surgery. We believe that CSA was triggered by the sudden variation in nocturnal arterial PCO2, which decreased from 52.3 mmHg before surgery to 42.0 mmHg after surgery. It is conceivable that, due to long-lasting severe OSAS, our patient lowered his chemosensitivity to PCO2. Consequently, the resolution of obstructive apnoeas and the restoration of normal nocturnal values of PCO2 may have reduced the nocturnal PCO2 to the point of being inadequate to stimulate ventilation.

Evaluation of pharyngeal muscle activity through nasopharyngeal surface electromyography in a cohort of dysphagic patients with acute ischaemic stroke.

Oro-pharyngeal dysphagia is frequently present during the acute phase of stroke. The aim of the present study was to evaluate whether the recording of surface EMG using a nasopharyngeal (NP) electrode could be applied to evaluation of pharyngeal muscle activity in acute stroke patients and if this neurophysiological measure is related with clinical assessment of swallowing. Patients were examined and clinical severity was assessed with the National Institute of Health Stroke Scale (NIHSS) score; dysphagia was evaluated through bedside screening test using the Gugging Swallowing Scale (GUSS). Extension of the ischaemic lesion was measured by quantitative score, based on CT scan [Alberta Stroke Programme Early CT Score (ASPECTS)]. We analysed 70 patients; 50 were classified as dysphagic (Dys+), and 20 as non-dysphagic (Dys-). Each participant underwent a surface NP EMG recording performed with a NP electrode, made of a Teflon isolated steel catheter, with a length of 16 cm and a tip diameter of 1.5 mm. The electrode was inserted through the nasal cavity, rotated and positioned approximately 3 mm anteroinferior to the salpingo-palatine fold. At least four consecutive swallowing-induced EMG bursts were recorded and analysed for each participant. Swallowing always induced a repetitive, polyphasic burst of activation of the EMG, lasting around 0.25 to 1 sec, with an amplitude of around 100-600mV. Two parameters of the EMG potentials recorded with the NP electrode were analyzed: duration and amplitude. The duration of the EMG burst was increased in Dys+ patients with a statistically significant difference compared to Dys- patients (p < 0.001). The amplitude was slightly reduced in the Dys+ group, but statistically significant differences were not observed (p = 0,775). Nevertheless, the burst amplitude showed a significant inverse correlation with NIHSS [r(48) = -0.31; p < 0.05] and ASPECTS scores [r(48) = -0.27; p < 0.05], meaning that the burst amplitude progressively reduced with an increase of clinical severity (NIHSS) and topographic extension of brain lesions in CT (ASPECTS). These results suggest that NP recordings can give a semi-quantitative measure of swallowing difficulties originating from pharyngeal dysfunction, in fact, electromyographic findings suggest reduced pharyngeal motility.

The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.

BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

Somatosensory system hyperexcitability in alternating hemiplegia of childhood.

BACKGROUND AND PURPOSE: Alternating hemiplegia of childhood (AHC) is a rare neurological disease characterized by recurrent paroxysmal attacks of hemiplegia. The aim of the study was to assess the recovery cycle of the somatosensory evoked potentials (SEPs) in a group of AHC patients. METHODS: Seven AHC patients and 10 control age-matched subjects (CS) were recruited. Right and left median nerve SEPs were recorded. The somatosensory system excitability was assessed by calculating the SEP changes after paired electrical stimuli. All patients were studied during the interictal phase, whilst four patients were studied also during the ictal phase. RESULTS: In AHC patients during the interictal phase, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30 responses showed a faster recovery than in CS. In AHC patients during the ictal phase, the cortical N20 recovery cycle was prolonged compared with the interictal phase. CONCLUSIONS: A shortened SEP recovery cycle in AHC during the interictal phase suggests multilevel somatosensory system hyperexcitability in AHC. A partial recovery of this phenomenon during the ictal phase possibly reflects a functional reset of the somatosensory system. Overall, there is a disinhibition of the somatosensory system in AHC, a functional change of brain function associated with a possible involvement of the Na(+) /K(+) channels. This abnormality and its partial recovery during the attacks might be linked to the pathophysiological and genetic mechanisms of the disease.

Pregnancy-induced analgesia: a combined psychophysical and neurophysiological study.

BACKGROUND: To investigate changes in heat pain threshold and modifications in heat pain processing during pregnancy and labour, seventy-six nulliparous pregnant women were enrolled in two studies. METHODS: In the first study (psychophysical), 60 pregnant women underwent a quantitative sensory testing (QST) investigating heat perception in two body areas (right forearm and T10 dermatome) according to these groups: 32-33 gestational weeks (GW), 39-40 GW, early stage of active labour and 24 h after the delivery. In the other study (neurophysiological), contact heat-evoked potentials (CHEPs) were recorded in other 16 women at the 32nd GW and in 11 of these also at the 40th GW. RESULTS: The psychophysical study showed that heat pain threshold was significantly increased at the forearm at 32-33 GW (median ± IQR: 39.6 ± 0.7 °C), at 39-40 GW (40.6 ± 1.1 °C) and at early stage of active labour (40.8 ± 1.5 °C) as compared to 20 non-pregnant controls (p < 0.001). Heat pain threshold tested at T10 level was significantly increased at 32-33 GW (41.0 ± 1.6 °C), at 39-40 GW (42.1 ± 1.8 °C), and at early stage of active labour (42.3 ± 1.3 °C) as compared to the non-pregnant women (p < 0.001). The N2-P2 CHEP amplitude (main negative N2 and positive P2 components of the vertex biphasic potential) recorded from the pregnant women was significantly lower at the 40th than at the 32nd GW, after stimulation of both the forearm (p < 0.001) and the abdomen (p < 0.001). CONCLUSIONS: In pregnant women, there is a progressive increase of heat pain threshold and a reduction of the CHEP amplitude, suggesting that a general inhibitory mechanism may be involved.

Evidence of different spinal pathways for the warmth evoked potentials.

OBJECTIVE: To investigate the presence of multiple spinothalamic pathways for warmth in the human spinal cord. METHODS: Laser evoked potentials to C-fiber stimulation (C-LEPs) were recorded in 15 healthy subjects after warmth stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels. This method allowed us to calculate the spinal conduction velocity (CV) in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different C-LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the C-N1 potential, generated in the second somatosensory (SII) area, and the late C-P2 response, generated in the anterior cingulate cortex (ACC). RESULTS: The calculated CV of the spinal fibers generating the C-N1 potential (around 2.5m/s) was significantly different (p<0.01) from the one of the pathway producing the P2 response (around 1.4m/s). CONCLUSIONS: Our results suggest that the C-N1 and the C-P2 components are generated by two parallel spinal pathways. SIGNIFICANCE: Warmth sensation is subserved by parallel spinothalamic pathways, one probably reaching the SII area, the other the ACC.

Congenital central hypoventilation syndrome: genotype-phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies.

The abnormal recovery cycle of somatosensory evoked potential components in children with migraine can be reversed by topiramate.

The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.

[Long-term effects on male gonadal function of antitumoral drugs used during childhood]. / Effetti sul sistema riproduttivo maschile dei farmaci antitumorali nei pazienti trattati in età pediatrica.

The survival rate of children and adolescents with cancer has improved dramatically in the last decades so that the prospect of survival in adulthood is today a realistic expectation for about 70% of the treated patients. However, the deleterious impact that chemotherapy and radiotherapy have on the reproductive function and future fertility could compromise the quality of life of the survivors in adulthood. The interest of the scientific community on this topic is increasing and focused on a more accurate evaluation of the reproductive risk among cancer treated children and on the development of less aggressive therapies. In the present review, some information about the long-term effects on the male reproductive function, particularly vulnerable to the cancer therapies, are reported from clinical and experimental studies. Furthermore, the concern about the development of pharmacological treatments and assisted reproductive techniques that might preserve or restore the fertility potential in children being treated with gonadotoxic cancer therapy, is discussed. These new strategies are still under experimentation and deeper knowledges on the functional development of the gonads during infancy, both in human and animals models are required. On the other hand, the future clinical application of these strategies in children rise important ethical and legal problems.

Dysfunction of arousal systems in sleep-related migraine without aura.

Primary headaches are closely related to sleep. Modifications in the patterns of arousal during sleep have been reported in migraine, especially in the nights preceding a headache attack. We aimed at evaluating the pattern of arousal from sleep in a group of patients affected by sleep-related migraine. We enrolled 10 consecutive patients, three males and seven females, aged between 20 and 62 years, who presented frequent attacks of migraine without aura (more than five per month), closely related to sleep (more than one-half of the attacks occurred during sleep, causing an awakening). A control group was studied, matched for age and sex. Patients and controls underwent a full-night polysomnographic study, following adaptation; arousal pattern was studied by the scoring of the high-frequency EEG arousal and by the cyclic alternating pattern (CAP). Migraineurs showed a lower CAP rate in non-rapid eye movement (NREM) sleep and, in particular, a lower number of A1 phases (low-frequency, high-amplitude EEG bursts) compared with the controls. Migraineurs also showed a lower index of high-frequency EEG arousals during rapid eye movement (REM) sleep. The reduction in the CAP rate indicates a lower level of arousal fluctuation in NREM sleep. The reduced arousal index in REM suggests a dysfunction in neural structures involved in both the control of REM sleep and the pathophysiology of migraine, such as the hypothalamus and the brainstem.

A sleep study in cluster headache.

Cluster headache (CH) is a primary headache with a close relation to sleep. CH presents a circa-annual rhythmicity; attacks occur preferably during the night, in rapid eye movement (REM) sleep, and they are associated with autonomic and neuroendocrine modifications. The posterior hypothalamus is the key structure for the biological phenomenon of CH. Our aim is to describe a 55-year-old man presenting a typical episodic CH, in whom we performed a prolonged sleep study, consisting of a 9-week actigraphic recording and repeated polysomnography, with evaluation of both sleep macrostructure and microstructure. During the acute bout of the cluster we observed an irregular sleep-wake pattern and abnormalities of REM sleep. After the cluster phase these alterations remitted. We conclude that CH was associated, in this patient, with sleep dysregulation involving the biological clock and the arousal mechanisms, particularly in REM. All these abnormalities are consistent with posterior hypothalamic dysfunction.

Multiple attack study on the available triptans in Italy versus placebo.

The aim of the study is to evaluate the efficacy and tolerability of the five triptans that are commercially available in Italy (zolmitriptan 2.5 mg, rizatriptan 10 mg, sumatriptan 100 mg, almotriptan 12.5 mg and eletriptan 40 mg). The study was conducted in single-blind versus placebo and its duration was 18 months. At the Headache Centre of the 'Agostino Gemelli' Hospital in Rome we selected 42 patients, suffering from headache with and without aura (International Headache Society Committee on Headache Classification, 1988 Cephalalgia 8:1-96), whose headache frequency ranged between 1- and 4-monthly crises. For a total of 25 crises, for every five consecutive crises, a different triptan was taken. The end-points of the study were as follows: response at 2 h, 'pain free' at 2 h and 'sustained pain free' (at 24 h). The intra-patient consistency and the tolerability were also evaluated. Thirty patients completed the study and the statistical analysis was only applied to these patients. No substantial difference in terms of the efficacy of the triptans was noted; all triptans were well tolerated. These results suggest the possibility of testing different triptans in the same patient in order to identify the ideal drug for every patient.

Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study.

The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.