ObjectiveSingle cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19.MethodsGBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered.ResultsIncidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002).ConclusionsThis study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

Several observations suggest impaired central sensory integration in dystonia. We studied median and ulnar nerve somatosensory evoked potentials (SEPs) in 10 patients who had dystonia involving at least one upper limb (six had generalized, two had segmental and two had focal dystonia) and in 10 normal subjects. We compared the amplitude of spinal N13, brainstem P14, parietal N20 and P27 and frontal N30 SEPs obtained by stimulating the median and ulnar nerves simultaneously (MU), the amplitude value being obtained from the arithmetic sum of the SEPs elicited by stimulating the same nerves separately (M + U). Throughout the somatosensory system, the MU : (M + U) ratio indicates the interaction between afferent inputs from the two peripheral nerves. No significant difference was found between SEP amplitudes and latencies for individually stimulated median and ulnar nerves in dystonic patients and normal subjects, but recordings in patients yielded a significantly higher percentage ratio [MU : (M + U)x100] for spinal N13 brainstem P14 and cortical N20, P27 and N30 components. The SEP ratio of central components obtained in response to stimulation of the digital nerves of the third and fifth fingers was also higher in patients than in controls but the difference did not reach a significant level. The possible contribution of subliminal activation was ruled out by recording the ratio of SEPs in six normal subjects during voluntary contraction. This voluntary contraction did not change the ratio of SEP suppression. These findings suggest that the inhibitory integration of afferent inputs, mainly proprioceptive inputs, coming from adjacent body parts is abnormal in dystonia. This inefficient integration, which is probably due to altered surrounding inhibition, could give rise to an abnormal motor output and might therefore contribute to the motor impairment present in dystonia.

Objectives-Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family hystory of dystonia, parkinsonism, and tremor. Methods-Cases aVected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and

The neurofilament light chain (NF-L) is a major constituent of intermediate filaments and plays a pivotal function in the assembly and maintenance of axonal cytoskeleton. Mutations in the NF-L gene (NEFL) cause autosomal dominant neuropathies that are classified either as axonal Charcot-Marie-Tooth (CMT) type 2E (CMT2E) or demyelinating CMT type 1F (CMT1F). The pathophysiological bases of the disorder(s) are elusive. We performed a mutational analysis of NEFL in a series of 177 index cases with CMT and without mutations in the genes for peripheral myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22) and connexin 32 (GJB1); the motor nerve conduction velocity (MNCV) at the median nerve was below 38 m/s in 76 cases and above 38 m/s in 101. We identified five new pedigrees with four mutations in the head and rod domains of NF-L, including a novel Leu268Pro substitution and a novel del322Cys_326Asn deletion. Several examined affected members exhibited marked variability in the severity of disease and age at onset. Nerve conduction alterations were consistent with an axonal neuropathy often associated with demyelinating features, such as prolonged distal latencies (DL). Pathological examination of sural nerve biopsies in the probands detected in four cases a chronic axonal neuropathy dominated by focal accumulations of NF with axonal swellings (giant axons) and significant secondary demyelination; in the fifth case no NFs accumulations were evident but many myelinated fibres consisted exclusively of microtubules with few or absent NF. The pathological phenotype correlated with the pattern of nerve conduction alterations and indicated that NEFL mutations cause a profound alteration of the cytoskeleton possibly related to defective targeting of NF.

Neurophysiological studies in animals show that basal ganglia are involved not only in motor and nonmotor timing functions but also in integrating tactile and visual signals delivered in the peripersonal space. We tested temporal discrimination of cross-modal and unimodal stimuli in 13 controls and 14 patients with writer's cramp, a disorder supposedly linked to dysfunction of basal ganglia. Subjects were asked to discriminate whether pairs of visual, tactile, or visuotactile stimuli were simultaneous or sequential (temporal discrimination threshold) and which stimulus preceded the other (temporal order judgment). Patients were impaired in temporal processing of tactile and cross-modal stimuli. A significant positive correlation between temporal deficits and the severity of disability was detected for both affected and unaffected sides. Findings suggest that multimodal and not only modality-specific temporal processing is defective in focal hand dystonia. Deficits of temporal processing of stimuli delivered to the unaffected side may represent a behavioral index of the susceptibility to develop dystonia and thus have remarkable practical and theoretical implications.

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Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contraction or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hypothesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism.

Clinical and experimental evidence documents abnormal somatosensory functions in dystonia. Despite the fact that somatosensory processing is inherently temporal, mainly spatial aspects of somatosensory functions have so far been assessed in dystonic patients. Seven patients with idiopathic dystonia and nine healthy controls were given pairs of non-noxious electrical stimuli separated by different time intervals and asked to report if they perceived single or double stimuli. Somesthetic temporal discrimination thresholds (STDT) were obtained by computing the shortest time interval at which stimuli, applied to the left or the right hand, were perceived as separate. STDT were significantly higher in dystonic than in controls thus showing for the first time that temporal and not only spatial somatosensory processing is altered in dystonia.