Manuello, J., Min, J., McCarthy, P. et al. The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease. Nat Commun15, 2576 (2024). https://doi.org/10.1038/s41467-024-46344-2
画像のキャプション： 図の左側、赤と黄色は、脳の他の部分よりも早く変性し、アルツハイマー病にかかりやすい領域を示している。 これらの脳領域は、さまざまな感覚から入ってくる情報を処理し、組み合わせる高次の領域である。 図の右側、各ドットはUKバイオバンク参加者1人の脳データを示す。 全体的な曲線は、脳のこれらの特に脆弱な領域では、加齢とともに変性が加速することを示している。 クレジット：G. Douaud and J. Manuello.
TREND研究（University of Tuebingen）では、PDのリスクが高い/低いn=1201人の2年に1度の血液サンプルが4年から10年にわたって前向きに採取された。 本研究では、後にPDと診断された12名の血液サンプルをレトロスペクティブに解析し、神経細胞外小胞由来の病的α-synコンフォーマーを、（1）これらのコンフォーマーに対する抗体を用いたイムノブロット解析、および（2）α-syn-SAAを用いて検出・増幅した。 さらに、TRENDコホートのn=13人の健常者とケルン大学病院のn=20人の孤立性急速眼球運動睡眠行動障害（iRBD）の血液サンプルを分析した。
Can we detect misfolded α-Synuclein in blood 10 years prior to a diagnosis of Parkinson's disease? Kluge, Berg and colleagues say YES in a just published small study in @MDJ_Journal. Key Points: – The authors cite the increasing importance of our ability to identify potential… pic.twitter.com/7yXt2soOEs
Can we detect misfolded α-Synuclein in blood 10 years prior to a diagnosis of Parkinson’s disease? Kluge, Berg and colleagues say YES in a just published small study in @MDJ_Journal. Key Points:
The authors cite the increasing importance of our ability to identify potential Parkinson’s in a prodromal phase.
They keyed in on a blood-based α-synuclein seed amplification assay.
They had access to biennial blood samples from 1201 folks taken over a period of 4 to 10 years (cohort was general with and without Parkinson’s).
They had available blood samples from 12 participants who were later diagnosed with PD; compared to 13 healthy controls and 20 w/ isolated rapid eye movement sleep behavior disorder (they got these last samples from another cohort).
The Parkinson’s cohort all manifested a positive seeding assay at diagnosis and 1-10 years prior to diagnosis.
The iRBD cohort had 30% α-syn seeding and none of the controls had seeding. My take: Although the number of samples was very small, the data was compelling that by amplifying pathological α-syn conformers in peripheral blood, the marker was present up to 10 years before the clinical diagnosis. This data reminds me of what was recently published by two independent Alzheimer’s groups showing markers were present (amyloid, tau) many years before diagnosis. The other important aspect to this study was the use of blood and not spinal fluid. It will be important for practicality and for global access that blood based biomarkers are further developed.
Why do female patients with AD have more pronounced tau pathology compared to males? Wang et al. provide evidence that amyloid modulates tau phosphorylation in a sex-specific manner, contributing to faster neurofibrillary tau accumulation in females. https://t.co/LNBpZWIz11pic.twitter.com/k48ZHbECmq
Who was the first author who described “midline splitting” as a sign for hystery？
The concept of “midline splitting” as a sign in functional neurological disorders was described in the context of functional limb weakness. It’s fascinating how these conditions can mimic other neurological issues, like stroke. Let me provide you with more details.
In a clinical vignette, a 35-year-old woman presented to the emergency room with sudden right-sided weakness during an argument with her partner. She described her right side as “heavy” and had difficulty speaking clearly. Her right arm dropped after 10 seconds of lifting, and she couldn’t lift her right leg at all. Interestingly, she also had complete loss of sensation in her right arm and leg. The neurological examination revealed facial asymmetry, give-way weakness, and a phenomenon known as Hoover’s sign1.
As for the first author who described this sign, I couldn’t find a specific historical reference. However, it’s essential to recognize that functional neurological disorders have evolved over time. In the nineteenth century, hysteria primarily manifested as motor symptoms like paralysis and fits. Later, sensory symptoms such as headache, backache, fatigue, and dizziness became more prominent3.
In summary, “midline splitting” is an intriguing sign associated with functional limb weakness, and it highlights the complexity of neurological diagnoses. While I don’t have a precise historical reference, understanding these phenomena helps clinicians differentiate between functional and organic causes. 😊
The hip abductor sign is similar to Hoover’s sign and describes weakness of voluntary hip abduction, which returns, through automatic movements, to normal during contralateral hip abduction against resistance24 (Figure). In a study of 33 patients with lateralized leg weakness (16 functional and 17 organic, of whom 8 with stroke), this sign achieved 100% sensitivity and specificity.24
Downward drift with pronation indicates cortical weakness. Drift without pronation is a typical finding in patients with functional arm weakness (Figure). In a study of 26 patients with functional arm weakness and 28 controls with organic paresis (23 due to stroke), drift without pronation identified functional arm weakness with a sensitivity of 100% (CI, 84%–100%) and a specificity of 93% (CI, 76%–98%).25
Functional motor disorders of the face are generally easy to distinguish from facial symptoms of stroke. The unilateral lip-pulling sign (Figure) reveals a characteristic functional dystonic movement disorder of the face that may give a superficial appearance of weakness but is actually caused by overactivity, typically of platysma or the muscles of jaw deviation.26Ipsilateral orbicularis oculis contraction may be an accompanying feature. Other facial or axial signs include the trunk-thigh test,27 which has a low interrater reliability,18 and the wrong-way tongue deviation away from paretic side28(toward hemiparesis in most strokes29), which remains to be evaluated systematically and can be false positive in medullary infarctions.30 The proposed sternocleidomastoid muscle test, in which head rotation is more likely to be weak toward the side of hemiparesis in patients with functional paresis,31 is problematic as it is documented as a common finding in stroke.32,33
In most cases, functional limb weakness is accompanied by sensory deficits. However, sensory testing in general has low interrater reliability,34,35 and most diagnostic signs that have been suggested for identifying functional sensory disturbance do not have the required specificity. For example, nonanatomic distributions of acute sensory symptoms, such as a glove-like distribution, are found in patients with distal arm paresis due to cortical stroke.36Another proposed feature of functional hemisensory disturbance is so-called midline splitting. Since cutaneous nerves of the trunk typically overlap a couple of centimeters at the midline, an exact splitting of deficits is often attributed to a functional disorder. However, midline splitting can be found in patients with clear organic causes of sensory loss,37–39particularly in pure sensory stroke, which can remain magnetic resonance imaging (MRI) negative.40 Other proposed signs for functional sensory symptoms, such as splitting of vibration sense (vibration is felt less on the numb side of the forehead or sternum despite intact bone conduction), similarly lack specificity for use in stroke workup.38,39 It should be noted that these clinical signs may show better specificity when combined with the above mentioned motor signs.16
In conclusion, clear positive signs of inconsistency of deficits should support the diagnosis of functional neurological disorder. Diagnosis based solely on psychosocial factors, psychiatric comorbidity, or negative imaging is not clinically indicated and a common source of error in the diagnosis of functional neurological disorder.41 Even minor symptoms that indicate acute cerebrovascular pathology, such as clear upper motor neuron facial weakness,21 should discourage acute diagnosis of a functional disorder.
34. Thaller M, Hughes T. Inter-rater agreement of observable and elicitable neurological signs.Clin Med (Lond). 2014; 14:264–267. doi: 10.7861/clinmedicine.14-3-264Google Scholar
35. Lindley RI, Warlow CP, Wardlaw JM, Dennis MS, Slattery J, Sandercock PA. Interobserver reliability of a clinical classification of acute cerebral infarction.Stroke. 1993; 24:1801–1804. doi: 10.1161/01.str.24.12.1801LinkGoogle Scholar
37. Chabrol H, Peresson G, Clanet M. Lack of specificity of the traditional criteria for conversion disorders.Eur Psychiatry. 1995; 10:317–319. doi: 10.1016/0924-9338(96)80314-2Google Scholar
38. Rolak LA. Psychogenic sensory loss.J Nerv Ment Dis. 1988; 176:686–687. doi: 10.1097/00005053-198811000-00007Google Scholar
39. Gould R, Miller BL, Goldberg MA, Benson DF. The validity of hysterical signs and symptoms.J Nerv Ment Dis. 1986; 174:593–597. doi: 10.1097/00005053-198610000-00003Google Scholar
Hysteria—Changing Concepts on the Nature of the Beast: Through Centuries
Neuropsychiatry Review The value of ‘positive’ clinical signs for weakness, sensory and gait disorders in conversion disorder: a systematic and narrative review Corinna Daum1, Monica Hubschmid2, Selma Aybek1 https://t.co/GLbzqeMOyl
Background: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear.
Methods: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% female) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073).
Results: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% female) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (males aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; females aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]).
Conclusions: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.
この結果は、軽症のCOVID-19から回復した患者にもSARS-CoV-2が残存している可能性があること、またウイルスの残存とCOVID症状の長期化には有意な関連があることを示唆している。 Long COVID症状との関連性を検証し、long COVID症状を改善するための潜在的な標的を同定するためには、さらなる研究が必要である。
Figure 2Detection of SARS-CoV-2 RNA in various solid tissue types at 1 month, 2 months, and 4 months after infection
Figure 5Differential characteristics of lung and blood vessel tissues with or without viral persistence revealed by transcriptome sequencing
ヒートマップは、肺（A）と血管（C）で発現が異なる遺伝子を示したもの。 肺組織には、感染1ヵ月後（サンプル125、114、112、120、70、116）、感染2ヵ月後（サンプル117、126、118、115、129、122）、感染4ヵ月後（サンプル127、119、113、121、123、124）に採取したウイルス陰性サンプルと、感染1ヵ月後（サンプル108）、感染2ヵ月後（サンプル109、111、105、106、107）に採取したウイルス陽性サンプルが含まれる。 血管組織には、感染2ヵ月後（サンプル98、100、132）と感染4ヵ月後（サンプル95、99）に採取されたウイルス陰性サンプルと、感染2ヵ月後（サンプル90、89、87、91、93）と感染4ヵ月後（サンプル88）に採取されたウイルス陽性サンプルが含まれる。 バブルプロットは、Kyoto Encyclopedia of Genes and Genomesのパスウェイ解析に基づき、肺組織サンプル（B）および血管（D）において、ウイルス持続性の有無にかかわらず発現が異なる遺伝子の濃縮パスウェイを示す。
Review ArticleThieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Functional (Psychogenic) Neurological Disorders: Assessment and Acute Management in the Emergency Department
Jordan R. Anderson, et al.
Functional Sensory Deficits
Functional sensory symptoms may be identified by neurologic examination and are often, but not exclusively, present with signs of functional weakness. Several “rule-in” signs have been identified in the literature for functional sensory deficits; however, not all are highly specific and thus they should be interpreted with caution.
Midline splitting is the loss of sensation of the entire body with a sharp demarcation at the midline, even on the trunk. This is considered functional since cutaneous branches of intercostal sensory nerves overlap from the contralateral side, making sensory loss from traditional neurological conditions occurring 1 or 2 cm from the midline. However, one exception is in the case of thalamic lesions from stroke or tumor, which may lead to midline truncal sensory splitting.[39] [42]
Vibratory splitting is another midline functional neurological sign, where vibration sensation is felt to differ from one side to the other and often suddenly changes at the midline when tested over a continuous bony prominence. As vibration is conducted through bone, if vibration sensation is tested on the forehead or the sternum, in general it should be perceived evenly on both sides. This test is sensitive (73.1–99.7%) but not very specific (7.3–23.7%)[39] [42] [43] and the phenomenon has been identified in other rare neurologic conditions (ischemic or hemorrhagic stroke involving ventroposterior thalamus,[44] [45] corona radiata,[46] paramedian dorsolateral pons,[47] lenticulocapsular region,[46] [48] and parietal lobe[49]); therefore, it should be used with caution.[43]
Nonanatomical (dermatomal) sensory loss is a heterogeneous phenomenon in which patterns of patient’s sensory loss do not fit a known neuroanatomical distribution. One study demonstrated 100% specificity of this finding for FND, although the finding was not well defined.[50] Classically reported nondermatomal sensory loss patterns include truncal symptoms with an anterior (but not posterior) level, sharply demarcated boundaries near the groin or shoulder, or unilateral stocking/glove as seen in [Fig. 2]. Inconsistency and non-reproducibility of the sensory examination findings is another commonly studied functional sensory sign.[40] [50] A different neurological condition such as stroke or tumor should produce relatively static sensory deficits. Logically, if sensory symptoms change throughout the exam, functional sensory loss may be considered. However, this may represent a pitfall as rapidly changing sensory symptoms may be present in conditions such as myelopathy, acute polyneuropathy, migraine, seizure, or transient ischemic attacks.[51]
Zand MS, Spallina S, Ross A, Zandi K, Pawlowski A, Seplaki CL, et al. (2024) Ventilation during COVID-19 in a school for students with intellectual and developmental disabilities (IDD). PLoS ONE 19(4): e0291840. doi:10.1371/journal.pone.0291840
ニューロドクター乱夢随想録 