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Abstract Background In patients with Parkinson’s disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn. Methods NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn. Results In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD. Conclusion In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.

Abstract Statin treatment has been associated with necrotizing autoimmune myopathy and has been linked to myasthenia gravis. We present an unprecedented clinical challenge with both disorders occurring in a patient treated with statins few months earlier.

Introduction: Cervical dystonia (CD) is one of the most common forms of adult-onset isolated dystonia. Recently, CD has been classified according to the site of onset and spread, in different clinical subgroups, that may represent different clinical entities or pathophysiologic subtypes. In order to support this hypothesis, in this study we have evaluated whether different subgroups of CD, that clinically differ for site of onset and spread, also imply different sensorimotor features.Methods: Clinical and demographic data from 842 patients with CD from the Italian Dystonia Registry were examined. Motor features (head tremor and tremor elsewhere) and sensory features (sensory trick and neck pain) were investigated. We analyzed possible associations between motor and sensory features in CD subgroups [focal neck onset, no spread (FNO-NS); focal neck onset, segmental spread (FNO-SS); focal onset elsewhere with segmental spread to neck (FOE-SS); segmental neck involvement without spread (SNI)].Results: In FNO-NS, FOE-SS, and SNI subgroups, head tremor was associated with the presence of tremor elsewhere. Sensory trick was associated with pain in patients with FNO-NS and with head tremor in patients with FNO-SS.Conclusion: The frequent association between head tremor and tremor elsewhere may suggest a common pathophysiological mechanism. Two mechanisms may be hypothesized for sensory trick: a gating mechanism attempting to reduce pain and a sensorimotor mechanism attempting to control tremor.

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rapidly evolving condition that combines psychiatric and neurologic manifestations. Much remains unclear about its clinical onset and subsequent course. Although successful treatment depends on diagnosing the disorder early and therefore minimizing long-term complications, this is a difficult task owing to the atypical onset of this condition and the prolonged clinical course that has been observed in some patients. This report, illustrating a patient with slowly progressing psychiatric manifestations, unusual imaging and electrophysiological features, extends the information on varied clinical phenotypes. Case Report: A 32-year-old woman suffered from an isolated depressive disorder for 4 months before undergoing psychiatric evaluation. During the following 5 months, she manifested hypersexuality, dysarthria, imbalance, dyskinesias and decreased word output. Brain magnetic resonance imaging (MRI) showed multifocal hyperintense T2/FLAIR lesions, a few contrast-enhanced, involving the corona radiata, the periventricular white matter, the deep gray nuclei, the optic nerves and the brainstem. MRI spectroscopy disclosed confluent bilateral demyelination and focal optic nerve involvement suggesting widespread encephalitis. Visual evoked potential studies indicated a demyelinating disorder. Serological screening and total body positron-emission tomography yielded negative findings for malignancies. Cerebrospinal fluid examination disclosed IgG oligoclonal bands and anti-NMDAR antibodies. Corticosteroids and intravenous immunoglobulin provided only slight improvement, whereas switching to cyclophosphamide markedly improved her neurological status. Conclusion: In patients with a prolonged clinical course, including psychiatric and neurological symptoms, the differential diagnosis should be anti-NMDAR encephalitis. This report expands the known disease phenotypes in this emerging condition.

An adult with Sandhoff disease presented with pure lower motor neuron phenotype. Twenty years later, he showed signs of upper motor neuron involvement. 25 years from the onset, his muscle weakness slightly worsened but he was fully independent in activities of daily living. GM2-gangliosidosis can manifest as a motor neuron disease with a slowly progressive course. The correct knowledge of the natural history can be really important to achieve the diagnosis, design new therapies and evaluate clinical trials.

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. [ABSTRACT FROM AUTHOR]

A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning–test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory–motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level. © 2003 Movement Disorder Society [ABSTRACT FROM AUTHOR]