Phantom limb pain (PLP) affects up to 80% of amputees. Despite the lack of consensus about the etiology and pathophysiology of phantom experiences, previous evidence pointed out the role of changes in motor cortex excitability as an important factor associated with amputation and PLP. In this systematic review, we investigated changes in intracortical inhibition as indexed by transcranial magnetic stimulation (TMS) in amputees and its relationship to pain. Four electronic databases were screened to identify studies using TMS to measure cortical inhibition, such as short intracortical inhibition (SICI), long intracortical inhibition (LICI) and cortical silent period (CSP). Seven articles were included and evaluated cortical excitability comparing the affected hemisphere with the non-affected hemisphere or with healthy controls. None of them correlated cortical disinhibition and clinical parameters, such as the presence or intensity of PLP. However, most studies showed decreased SICI in amputees affected hemisphere. These results highlight that although SICI seems to be changed in the affected hemisphere in amputees, most of the studies did not investigate its clinical correlation. Thus, the question of whether they are a valid diagnostic marker remains unanswered. Also, the results were highly variable for both measurements due to the heterogeneity of study designs and group comparisons in each study. Although these results underscore the role of inhibitory networks after amputation, more studies are needed to investigate the role of a decreased inhibitory drive in the motor cortex to the cause and maintenance of PLP.

Background: Autoimmune encephalitis (AIE) is the main differential diagnosis of infectious encephalitis. Brain MRI is normal in up to 50% of cases and studies indicate that changes in FDG-PET/CT are more frequent and early. Objectives: To describe FDG-PET/CT findings in patients with AIE of Hospital Israelita Albert Einstein (HIAE) from 2015-2020. Design and setting: Retrospective cross-sectional study at HIAE. Methods: Medical records of patients with suspected AIE were reviewed. Laboratory results were compiled, and images were reassessed. Results: Amongst 250 records, we found 7.6% (n=19) of AIE, being 8 seropositive (5 anti-NMDA, 1 anti-CASPR2, 1 anti-MOG, 1 anti-VGKC and 1 anti-LGI1), 5 seronegative and 4 limbic encephalitis. The mean age was 48-22 years, 52% male. In encephalitic patients, the most common manifestations were epilepsy (78%), cognitive changes (63%), and behavioral changes (63%). Only 57% had abnormal MRI. We evaluated 23 PET/CTs at different stages of treatment; of the 9 FDG-PET/CTs performed at initial presentation, 88% were abnormal and 30% had normal MRI. Most frequent patterns found were hypometabolism in frontal (59.1%), temporal (39.1%) and left parietal (39.1%) regions. In follow-up, only 2 patients normalized FDG-PET/CT, with clinical improvement. Conclusions:FDG-PET/CT was altered in 88% of patients. In this series, no typical PET/CT pattern was demonstrated for AIE; the most frequent findings were hypometabolism in cortical areas, which also occur in degenerative diseases. We did not find hypermetabolism, or mixed areas of hypo- and hypermetabolism. The specificity of PET/CT for AIE diagnosis should be evaluated in future studies.

Context: Severe neurological manifestations following use of immune checkpoint inhibitors (ICIs) occur in 0.93% of patients, and together with cardiac toxicity have the higher lethality. Myasthenia gravis (MG) and polymyositis (PM) are rare, and treatment includes discontinuation of the immunotherapy, corticosteroids, and intravenous immunoglobulin (IVIG), with occasional use of plasmapheresis (PLEX). Biomarkers are not consistently reported. We report the case of a patient with MG, PM and myocarditis after ICI, with positive anti-titin antibodies and response to plasmapheresis. Case report: 81-year-old male developed ascending, subacute, progressive tetraparesis, dysphagia, ophthalmoparesis, and respiratory failure 2 weeks after second cycle of nivolumab/ipilimumab for metastatic melanoma. Physical examination showed: globally reduced strength, hypoactive reflexes, bilateral sixth nerve palsy and bilateral semi-ptosis. Prostigmine test was positive and electroneuromyography was compatible with myopathy. Labs revealed CPK 4000 U/L, troponin 9000U/L, autoimmune myositis panel negative, anti-titin antibodies (described in paraneoplastic MG and associated with severity) positive and cardiac MRI without fibrosis. Clinical picture was compatible with MG and PM with cardiac involvement. He received methylprednisolone and six PLEX sessions, with complete recovery. Four months after treatment, he developed cognitive impairment and large B-cell lymphoma (ICI complication). Conclusions: PM and MG may occur after ICI, especially in the first cycles, and anti-titin may be a biomarker of severity in these patients. Although guidelines recommend adding IVIG or PLEX in refractory or severe cases, PLEX may be first choice, especially if multiple ICI are present.