Small fibre neuropathy (SFN), a condition dominated by neuropathic pain, is frequently encountered in clinical practise either as prevalent manifestation of more diffuse neuropathy or distinct nosologic entity. Aetiology of SFN includes pre-diabetes status and immune-mediated diseases, though it remains frequently unknown. Due to their physiologic characteristics, small nerve fibres cannot be investigated by routine electrophysiological tests, making the diagnosis particularly difficult. Quantitative sensory testing (QST) to assess the psychophysical thresholds for cold and warm sensations and skin biopsy with quantification of somatic intraepidermal nerve fibres (IENF) have been used to determine the damage to small nerve fibres. Nevertheless, the diagnostic criteria for SFN have not been defined yet and a ‘gold standard’ for clinical practise and research is not available. We screened 486 patients referred to our institutions and collected 124 patients with sensory neuropathy. Among them, we identified 67 patients with pure SFN using a new diagnostic ‘gold standard’, based on the presence of at least two abnormal results at clinical, QST and skin biopsy examination. The diagnosis of SFN was achieved by abnormal clinical and skin biopsy findings in 43.3% of patients, abnormal skin biopsy and QST findings in 37.3% of patients, abnormal clinical and QST findings in 11.9% of patients, whereas 7.5% patients had abnormal results at all the examinations. Skin biopsy showed a diagnostic efficiency of 88.4%, clinical examination of 54.6% and QST of 46.9%. Receiver operating characteristic curve analysis confirmed the significantly higher performance of skin biopsy comparing with QST. However, we found a significant inverse correlation between IENF density and both cold and warm thresholds at the leg. Clinical examination revealed pinprick and thermal hypoesthesia in about 50% patients, and signs of peripheral vascular autonomic dysfunction in about 70% of patients. Spontaneous pain dominated the clinical picture in most SFN patients. Neuropathic pain intensity was more severe in patients with SFN than in patients with large or mixed fibre neuropathy, but there was no significant correlation with IENF density. The aetiology of SFN was initially unknown in 41.8% of patients and at 2-year follow-up a potential cause could be determined in 25% of them. Over the same period, 13% of SFN patients showed the involvement of large nerve fibres, whereas in 45.6% of them the clinical picture did not change. Spontaneous remission of neuropathic pain occurred in 10.9% of SFN patients, while it worsened in 30.4% of them.

Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility, and interpretation of results. A consensus meeting was convened by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) to formulate recommendations for conducting QST in clinical practice and research. Research studies have confirmed the utility of QST for the assessment and monitoring of somatosensory deficits, particularly in diabetic and small fiber neuropathies; the assessment of evoked pains (mechanical and thermal allodynia or hyperalgesia); and the diagnosis of sensory neuropathies. Promising applications include the assessment of evoked pains in large-scale clinical trials and the study of conditioned pain modulation. In clinical practice, we recommend the use QST for screening for small and large fiber neuropathies; monitoring of somatosensory deficits; and monitoring of evoked pains, allodynia, and hyperalgesia. QST is not recommended as a stand-alone test for the diagnosis of neuropathic pain. For the conduct of QST in healthy subjects and in patients, we recommend use of predefined standardized stimuli and instructions, validated algorithms of testing, and reference values corrected for anatomical site, age, and gender. Interpretation of results should always take into account the clinical context, and patients with language and cognitive difficulties, anxiety, or litigation should not be considered eligible for QST. When appropriate standards, as discussed here, are applied, QST can provide important and unique information about the functional status of somatosensory system, which would be complementary to already existing clinical methods.

No abstract

Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P <0.001); intracerebral hemorrhages decreased from 400 to 322 (hospitalization RR, 0.81 [95% CI, 0.69–0.93]; P =0.004), and transient ischemic attacks decreased from 322 to 196 (hospitalization RR, 0.61 [95% CI, 0.51–0.73]; P <0.001). Hospitalizations decreased in Northern, Central, and Southern Italy. Intravenous thrombolyses decreased from 531 (22.1%) in 2019 to 345 in 2020 (19.1%; RR, 0.86 [95% CI, 0.75–0.99]; P =0.032), while primary endovascular procedures increased in Northern Italy (RR, 1.61 [95% CI, 1.13–2.32]; P =0.008). We found no correlation ( P =0.517) between the hospitalization RRs for all strokes or transient ischemic attack and COVID-19 incidence in the different areas. Conclusions: Hospitalizations for stroke or transient ischemic attacks across Italy were reduced during the worst period of the COVID-19 outbreak. Intravenous thrombolytic treatments also decreased, while endovascular treatments remained unchanged and even increased in the area of maximum expression of the outbreak. Limited hospitalization of the less severe patients and delays in hospital admission, due to overcharge of the emergency system by COVID-19 patients, may explain these data.

No abstract

When botulinum toxin (BT) is administered for the first time at fixed doses, variable clinical responses can be observed in patients with the same form of dystonic disorder. Many factors may contribute to this phenomenon, including the variability rate of absorption of the drug. Animal experimental models (rat diaphragm preparation) have demonstrated an increased absorption of BT in the terminal nerve endings of the muscle under repetitive electrical stimulation, suggesting that "muscle activity" also may play an important role. The aim of our study was to evaluate in humans the role of the muscle activity on the variability of the effect induced by BT type A. Eleven patients with blepharospasm and idiopathic facial hemispasm were studied by using neurophysiologic techniques. In nine patients, both extensor digitorum brevis (EDB) muscles were injected with low (3 IU), fixed doses of type A BT. For the first 24 h after administration of the drug, periodic electrical stimulation of only one EDB was used. The subsequent percentage changes in compound muscle action potential (CMAP) amplitude was calculated at different intervals over a 30-day period. The percentage in the CMAP for the stimulated EDB was compared with that of the contralateral nonstimulated side. We found that the effect of the induced neuromuscular blockade was significantly greater for the stimulated side. In the other two patients, we injected BT in one EDB and the same volume of normal saline solution in the contralateral muscle to assess the stability of the CMAP in untreated muscle over time. We observed that the CMAP was unchanged in the untreated EDB; therefore we concluded that muscle activity plays an important role in the variability of clinical response often seen.

In humans, botulinum neurotoxin (BoNT) serotype A (BoNT/A) is a useful therapeutic tool, but different BoNT serotypes may be useful when a specific immune resistance related to BoNT/A is proved. BoNT serotype F (BoNT/F) was injected into human muscles but its effects are shorter compared to BoNT/A, whereas BoNT serotype B (BoNT/B) is effective in humans only if injected at very high doses. BoNT serotype C (BoNT/C) has a general profile of action similar to BoNT/A. Nevertheless, a comparison between these different BoNTs in human has not yet been reported. To establish the general profile of these different BoNTs in humans and the spread in near and untreated muscles we conducted an electrophysiological evaluation in 12 healthy volunteers by injecting BoNT/A (BOTOX 15MU), BoNT/B (NeuroBloc 1500MU), BoNT/F (15MU), BoNT/C (15MU) and a saline solution (placebo) in the abductor digiti minimi muscle (ADM) in a double-blind manner. The compound muscle action potential (CMAP) amplitude variation, before and at 2, 4, 6 and 8 weeks after the injections, was evaluated in the ADM, the fourth dorsal interosseus, the first dorsal interosseus and the abductor pollicis brevis APB. We detected an earlier recovery for BoNT/F when compared to the other BoNTs. No significant differences in the local or distant BoNT spread was observed among the different serotypes. We conclude that in humans, BoNT/B and BoNT/C have a general profile similar to BoNT/A and as such these serotypes could be alternative therapies to BoNT/A. BoNT/F might be useful when only a short duration of neuromuscular blockade is required.

To evaluate nervous system involvement in a cohort of Italian patients with primary Sjögren's syndrome (pSS), 87 unselected patients (83 female, and four male) observed consecutively at our institution over a period of 5 years were screened by clinical and instrumental (MRI, SPECT, electrophysiological testing, CSF analysis) investigations for peripheral and central neurological abnormalities. Seroimmunological parameters and extraglandular features other than neurological manifestations were also evaluated. Seven patients had central nervous system (CNS) disease (8%), mostly non-focal dysfunction, and 12 had peripheral nervous system (PNS) disease (13.8%), mostly mild or severe sensory or sensory-motor polyneuropathies. One patient had concomitant CNS and PNS involvement. Compared with CNS disease, PNS involvement occurred in older patients (> 50 years), independent of the disease duration. Patients with and without neurological abnormalities did not differ for seroimmunological parameters (including antiphospholipid antibodies) or extraglandular manifestations. From a statistical point of view, the only relevant finding was the detection of a slight increase in serum IgA and IgM levels (p < 0.05) in patients with an intact nervous system. Neurological involvement in pSS, be it central or peripheral, is not a rare finding. A careful clinical neurological evaluation, combined with a multiplicity of instrumental investigations, is recommended in the global assessment of pSS patients.