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Background: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and eyelid spasms. Studies have shown the presence of sensory deficits associated with dystonia. Aim: To rule out any confounding effect of muscle spasms on sensory performance in affected and unaffected body regions of patients with blepharospasm and with hemifacial spasm. Methods: Participants (19 patients with blepharospasm, 19 patients with hemifacial spasm and 19 control subjects) were asked to discriminate between two stimuli that were either simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 ms (in 10-ms steps) to the hands or on the skin over the orbicularis oculi muscle. Results: Tactile stimuli elicited similar TDTs in control subjects and patients with hemifacial spasm, but significantly higher TDTs in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. Conclusions: As TDT was abnormal in unaffected body regions of patients with blepharospasm, and patients with hemifacial spasm processed tactile stimuli normally, TDT deficits in blepharospasm depend on central rather than peripheral factors. This study further supports the link between focal dystonia and impaired temporal processing of somatosensory inputs. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes., Methods: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS., Results: Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes., Conclusion: Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: The optimal management for immune-related adverse events (irAEs) in patients who do not respond or become intolerant to steroids is unclear. Guidelines suggest additional immunosuppressants on the basis of case reports and expert opinion., Methods: We evaluated patients with lung cancers at Memorial Sloan Kettering Cancer Center treated with immune checkpoint blockade from 2011 to 2020. Pharmacy records were queried to identify patients who received systemic steroids and an additional immunosuppressant (e.g., tumor necrosis factor-α inhibitor, mycophenolate mofetil). Patient records were manually reviewed to evaluate baseline characteristics, management, and outcomes., Results: Among 2750 patients with lung cancers treated with immune checkpoint blockade, 51 (2%) received both steroids and an additional immunosuppressant for a severe irAE (tumor necrosis factor-α inhibitor (73%), mycophenolate mofetil (20%)). The most common events were colitis (53%), pneumonitis (20%), hepatitis (12%), and neuromuscular (10%). At 90 days after the start of an additional immunosuppressant, 57% were improved from their irAE, 18% were unchanged, and 25% were deceased. Improvement was more common in hepatitis (five of six) and colitis (18 of 27) but less common in neuromuscular (one of five) and pneumonitis (3 of 10). Of the patients who died, 8 of 13 were attributable directly to the irAE and 4 of 13 were related to toxicity from immunosuppression (three infection-related deaths, one drug-induced liver injury leading to acute liver failure)., Conclusions: Steroid-refractory or resistant irAEs events are rare. Although existing treatments help patients with hepatitis and colitis, many patients with other irAEs remain refractory or experience toxicities from immunosuppression. A more precise understanding of the pathophysiology of specific irAEs is needed to guide biologically-informed treatments for severe irAEs., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: More than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT., Methods: We retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks., Results: Forty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group., Conclusions: Greater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-116). The authors have no conflicts of interest to declare, (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Aim : to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies.. Design: Multi-center cross-sectional observational study. Setting : 23 intensive neurorehabilitation units. Subjects : 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury. Main Measures : Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications. Results : patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology. Conclusion : overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Post-streptococcal neuropsychiatric disorders encompass a broad spectrum of movement disorders, including tics, stereotypies, dystonia and tremor. We report the case of a 15-year-old boy who presented with a relapsing-remitting combination of psychogenic and organic movement disorders. Both relapses occurred after an episode of streptococcal pharyngitis and consisted in motor and phonic tics, an atypical gait disorder, and severe worsening of a pre-existing psychogenic tremor of the right hand. After each relapse, both psychogenic and 'organic' symptoms concomitantly remitted after the administration of an association of oral steroids and antibiotics. The peculiarity of this case consists in the coexistence of psychogenic and organic symptoms subsequent to streptococcal infection, and broadens the clinical spectrum of post-streptococcal neuropsychiatric disorders.

Aim: The level of daily life autonomy in patients with stroke may be related to recovery of affected arm function. The aim of the study was to assess whether four simple bedside indexes of arm recovery can predict levels of autonomy in daily life activities., Methods: A consecutive sample of 48 patients presenting with upper limb paresis/plegia in the acute stage after stroke was selected. Patients underwent five evaluation sessions at 7, 14, 30, 90 and 180 days after stroke. Forward stepwise multiple regression analysis was used to clarify the role of four potential predictors of upper limb recovery (active finger extension, shoulder abduction, shoulder shrug and hand movement scales). Dependent variables in these models were the Barthel Index score and sub-items of the Burke-Fahn-Marsden Scale., Results: The active finger extension scale showed a highly significant statistical correlation with patient performance in nearly all outcome measures. The shoulder shrug correlated with the BI score, and with the dressing and hygiene Burke-Fahn-Marsden Scale sub-items. Shoulder abduction and hand movement scale played only a minor role., Conclusions: The active finger extension scale proved to be a strong early predictor of recovery of daily life autonomy in patients with stroke. This finding could be important in order to planning a specific rehabilitation treatment after the onset.

DYT1 primary torsion dystonia is an autosomal dominant movement disorder due to a 3-bp GAG deletion in the TOR1A gene, which becomes manifest in only 30-40% of mutation carriers. Investigating the factors regulating this reduced penetrance might add new insight into the mechanisms underlying the disease. The pathophysiology of dystonia has been related to basal ganglia dysfunctions that lead to the most prominent motor symptoms. However, subclinical sensory deficits have also been reported, particularly in adult-onset focal dystonia. Sensory abnormalities in different forms of sporadic dystonia have been revealed by using a psychophysical method, namely, the temporal discrimination threshold (TDT), quantified as the shortest time interval at which the two stimuli are perceived as separate. Little or no information about the presence of sensory abnormalities in DYT1 gene manifesting and non-manifesting carriers is available. With the aim of disclosing possible associations between sensory deficits and the DYT1 mutation, we assessed TDTs of DYT1 manifesting patients (n = 9); DYT1 non-manifesting relatives (n = 11); non-carrier relatives (n = 9); external control subjects (n = 11). Pairs of tactile, visual or visuo-tactile stimuli were delivered in blocked, counterbalanced order. Intervals between stimuli increased from 0 to 400 ms (in 10 ms steps). On each trial, subjects had to report whether stimuli occurred simultaneously or asynchronously. We measured the first out of three consecutive inter-stimulus intervals at which subjects recognized the two stimuli as temporally separated (TDT) and the first of three consecutive intervals at which they also reported correctly which stimulus in the pair preceded (or followed) the other temporal order judgment (TOJ). Results showed higher tactile and visuo-tactile TDTs and TOJs in DYT1 carriers, both manifesting and non-manifesting, compared with non-carrier relatives and with external control subjects (for all comparisons, P < 0.039). This finding indicates that the DYT1 mutation determines subclinical sensory alterations, which could be disclosed by a psychophysical task. Moreover, these results have the notable implication that sensory deficits in dystonia are not a mere consequence of abnormal movements, but they may even occur before overt clinical manifestations, representing a subclinical phenotype in DYT1 mutation carriers.

The GAG deletion in the DYT1 gene usually causes a typical form of primary torsion dystonia (PTD) with early onset in a limb, rapid generalization, and sparing of cranial-cervical muscles, but atypical phenotypes have often been reported. Here, we describe a large DYT1 Italian family with phenotypically heterogeneous PTD that recapitulates all the atypical features associated with the DYT1 mutation, including late age at onset, focal or segmental phenotypes, onset or spreading of dystonia to the cranial-cervical muscles. Of 38 healthy family members, 15 also carried the DYT1 mutation, with an estimated penetrance of 21%. A literature review of atypical familial cases of DYT1-PTD showed that late onset, cervical involvement, and limited progression of dystonia are features frequently seen in DYT1 families. However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia.

We report on a patient affected by Parkinson's disease who developed over a period of a few weeks a tonic deviation of her head, neck, and trunk fitting the typical description of Pisa syndrome (PS). This patient was under stable levodopa and pramipexole treatment and had never been exposed to any psychotropic or antiemetic drugs before or at the time she developed the postural abnormality. Because dopamine transporter imaging revealed bilateral and symmetrical reduction of striatal uptake, we suggest that PS is not primarily related to side differences in dopaminergic denervation or drug exposure., (Copyright (c) 2005 Movement Disorder Society.)