18letý chlapec s epilepsií a multifokální motorickou neuropatií po očkování proti chřipce byl přijat k hospitalizaci pro respirační infekci a stav po epileptickém paroxysmu. Při přijetí byl klinický nález až na chabou paraparézu dolních končetin jako reziduum multifokální neuropatie a faryngitidu chudý, laboratorně byla trombopenie a elevace zánětlivých markerů. Za 36 hodin od přijetí se rozvíjí kvalitativní porucha vědomí charakteru deliria s halucinacemi, bludy, poruchou paměti, výrazným motorickým neklidem a spánkovou inverzí. Chlapec byl následně přeložen na jednotku intenzivní péče. Bylo provedeno toxikologické a neurologické vyšetření s lumbální punkcí, MR i CT mozku, vše s negativním nálezem, psychiatrické vyšetření se závěrem organické delirium. Chlapec byl i přes vysoké dávky midazolamu, chlorpromazinu a risperidonu stále delirantní. Až po opakovaných rozhovorech chlapec přiznává abúzus alkoholu, zejména absintu, to potvrzuje i vysoká hladina CDT. Po nasazení klomethiazolu příznaky deliria rychle ustoupily.
An 18-year-old boy with epilepsy and multifocal motor neuropathy after influenza vaccination was admitted for respiratory infection and after an epileptic seizure. On admission, clinical findings were poor except for peripheral paraparesis as residual multifocal neuropathy and pharyngitis, with thrombopenia and elevation of inflammatory markers in the admission laboratory. Within 36 hours, he developed a qualitative disruption of consciousness in the nature of delirium with hallucinations, delusions, memory impairment, marked motor restlessness, and sleep inversion. The boy was subsequently transferred to the intensive care unit. Toxicological and neurological examination with lumbar puncture, MRI and CT of the brain were performed, all with negative findings, and psychiatric examination concluded organic delirium. The boy was still delirious despite high doses of midazolam, chlorpromazine and risperidone. Only after repeated interviews did the boy admit to alcohol abuse, especially absinthe, as confirmed by a high CDT level. After the administration of clomethiazole, the symptoms of delirium quickly subsided.
- MeSH
- Alcohol Withdrawal Delirium * etiology complications MeSH
- Chlorpromazine pharmacology therapeutic use MeSH
- Epilepsy drug therapy MeSH
- Respiratory Tract Infections drug therapy MeSH
- Carbohydrate Dehydrogenases analysis MeSH
- Humans MeSH
- Midazolam pharmacology therapeutic use MeSH
- Adolescent * MeSH
- Polyneuropathies etiology MeSH
- Consciousness Disorders etiology MeSH
- Risperidone pharmacology therapeutic use MeSH
- Seizures * etiology MeSH
- Check Tag
- Humans MeSH
- Adolescent * MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 Mb tandem duplication of chromosome 17 harbouring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To obtain better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22 duplication in cellular homeostasis in CMT1A mouse models and in patient-derived induced pluripotent stem cells differentiated into Schwann cell precursors (iPSC-SCPs). We performed lipidomic profiling and bulk RNA sequencing (RNA-seq) on sciatic nerves of two developing CMT1A mouse models and on CMT1A patient-derived iPSC-SCPs. For the sciatic nerves of the CMT1A mice, cholesterol and lipid metabolism was downregulated in a dose-dependent manner throughout development. For the CMT1A iPSC-SCPs, transcriptional analysis unveiled a strong suppression of genes related to autophagy and lipid metabolism. Gene ontology enrichment analysis identified disturbances in pathways related to plasma membrane components and cell receptor signalling. Lipidomic analysis confirmed the severe dysregulation in plasma membrane lipids, particularly sphingolipids, in CMT1A iPSC-SCPs. Furthermore, we identified reduced lipid raft dynamics, disturbed plasma membrane fluidity and impaired cholesterol incorporation and storage, all of which could result from altered lipid storage homeostasis in the patient-derived CMT1A iPSC-SCPs. Importantly, this phenotype could be rescued by stimulating autophagy and lipolysis. We conclude that PMP22 duplication disturbs intracellular lipid storage and leads to a more disordered plasma membrane owing to an alteration in the lipid composition, which might ultimately lead to impaired axo-glial interactions. Moreover, targeting lipid handling and metabolism could hold promise for the treatment of patients with CMT1A.
- MeSH
- Cell Membrane * metabolism MeSH
- Charcot-Marie-Tooth Disease * genetics metabolism pathology MeSH
- Gene Duplication MeSH
- Homeostasis * physiology MeSH
- Induced Pluripotent Stem Cells * metabolism MeSH
- Humans MeSH
- Lipid Metabolism * physiology MeSH
- Myelin Proteins * metabolism genetics MeSH
- Mice MeSH
- Sciatic Nerve metabolism MeSH
- Schwann Cells * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Na podkladě fyzikálních příčin vznikají v pracovní zátěži mononeuropatie (úžinové syndromy i komprese periferních nervů) i polyneuropatie. Nejčastějším fyzikální vlivem je přetížení, dále následuje expozice vibracím přenášeným na horní končetiny, ale také chlad, vlhko, nepříznivá pracovní poloha, tlak na nerv proti tvrdé podložce. Úžinové syndromy i zevní komprese periferního nervu vedou k ischemii fasciklů i jednotlivých axonů, k rozvoji edému, k poruše venózního odtoku, k vzestupu tlaku v úžině a nakonec i k fokální demyelinizaci či axonální lézi. Nadlimitní vibrace přenášené na horní končetinu vedou ke spazmům arteriol, k ischemii tkáně na akru HK, k poškození senzitivních a pak i motorických vláken a k rozvoji vibrační neuropatie. Důležité je klinické a elektrofyziologické zhodnocení. Následuje léčba a komplexní preventivní opatření.
Mononeuropathies (entrapment syndromes and compressions of peripheral nerves) and polyneuropathies develop during occupational exposition on the ground of physical reasons. The most common physical impact is overload, followed by exposition to vibrations transmitted to upper extremities, then cold, humidity, unfavorable position in work, and pressure on the nerve against a hard structure. Entrapment syndromes and outer compressions of peripheral nerves lead to the ischemic changes of fascicles and single axons, to development of oedema, to failure of the venous outflow, to the increase of pressure in entrapment and lastly to the focal demyelinization or axonal lesion. Over-limit vibration transferred via the upper extremity cause spasms of arteriols, leading to the tissue ischemia at the terminal structures of hand and fingers, to lesion of sensitive and later of motor nerve fibres and to the development of vibration neuropathy. Clinical and electrophysiological evaluation of these disorders is important. Treatment and the complex prophylactic measures follow.
- MeSH
- Electrodiagnosis methods MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Occupational Diseases diagnosis prevention & control MeSH
- Polyneuropathies MeSH
- Carpal Tunnel Syndrome diagnosis etiology therapy MeSH
- Nerve Compression Syndromes * diagnosis etiology therapy MeSH
- Tendon Entrapment MeSH
- Check Tag
- Humans MeSH
- MeSH
- Humans MeSH
- Myasthenia Gravis diagnosis etiology therapy MeSH
- Cranial Nerve Diseases diagnosis etiology therapy MeSH
- Small Fiber Neuropathy diagnosis etiology therapy MeSH
- Polyneuropathies diagnosis etiology therapy MeSH
- Lupus Vasculitis, Central Nervous System * diagnosis therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in patients with diabetes mellitus to study whether these could differentiate patients with and without pain and neuropathy. METHODS: A standardized QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n = 220) and non-painful distal symmetric polyneuropathy (nDSPN; n = 219), diabetic patients without neuropathy (DM; n = 23) and healthy non-diabetic subjects (n = 37). Based on the QST findings, diabetic subjects were further stratified into four predefined prototypic phenotypes: sensory loss (SL), thermal hyperalgesia (TH), mechanical hyperalgesia (MH) and healthy individuals. RESULTS: Patients in the pDSPN group showed the greatest hyposensitivity ('loss of function'), and DM patients showed the lowest, with statistically significant increases in thermal, thermal pain, mechanical and mechanical pain sensory thresholds. Accordingly, the frequency of the SL phenotype was significantly higher in the pDSPN subgroup (41.8%), than expected (p < 0.0042). The proportion of 'gain of function' abnormalities was low in both pDSPN and nDSPN patients without significant differences. CONCLUSIONS: There is a continuum in the sensory profiles of diabetic patients, with a more pronounced sensory loss in pDSPN group probably reflecting somatosensory nerve fibre degeneration. An analysis of 'gain of function' abnormalities (allodynia, hyperalgesia) did not offer a key to understanding the pathophysiology of spontaneous diabetic peripheral neuropathic pain. SIGNIFICANCE: This article, using quantitative sensory testing profiles in large cohorts of diabetic patients with and without polyneuropathy and pain, presents a continuum in the sensory profiles of diabetic patients, with more pronounced 'loss of function' abnormalities in painful polyneuropathy patients. Painful diabetic polyneuropathy probably represents a 'more progressed' type of neuropathy with more pronounced somatosensory nerve fibre degeneration. The proportion of 'gain of function' sensory abnormalities was low, and these offer limited understanding of pathophysiological mechanisms of spontaneous neuropathic pain.
Nepříjemné pocity aker končetin patří mezi velmi časté subjektivní potíže dospělých pacientů. Tato výpověď správně vede k suspekci na postižení periferních nervů - neuropatie. Cílem práce je upozornit praktické lékaře na další specifická anamnestická data a klinické projevy neuropatií, nápomocné pro stanovení úrovně postižení periferního nervu, rozsahu a typu neurogenní léze. Nabízíme návod k rozeznání pacientů s neuropatií a účelné formulaci žádosti o diagnostické a léčebné služby neurologa. Chceme praktické lékaře zevrubně seznámit s možnostmi elektromyografie, která je u těchto diagnóz stěžejní.
Unpleasant feelings in the limbs are a common occurrence in adult patients. In some cases, it may be indicative of peripheral nerve damage ie. neuropathy. This work aims to raise awareness of its symptoms and anamnestic circumstances among general practitioners and allow them to more accurately determine the kind and scope of damage to the nerve. We offer a guide for recognizing such patients and transferring them to the care of specialized neurologists. We would like to thoroughly introduce a diagnostic technique integral to correct assessment of the condition of peripheral nerves - electromyography. This article does not aim to describe individual clinical entities.
- MeSH
- Humans MeSH
- Mononeuropathies etiology classification physiopathology MeSH
- Motor Neurons physiology pathology MeSH
- Nerve Fibers MeSH
- Brachial Plexus Neuropathies classification physiopathology MeSH
- Peripheral Nervous System * anatomy & histology physiology physiopathology MeSH
- Peripheral Nerves anatomy & histology physiology MeSH
- Polyneuropathies etiology classification physiopathology MeSH
- Radiculopathy classification physiopathology MeSH
- Somatosensory Disorders classification MeSH
- Muscular Atrophy, Spinal diagnosis etiology physiopathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Úvod: Neuropatická bolest je častým klinickým projevem řady neurologických onemocnění. Klíčovou součástí jejího diagnostického algoritmu jsou jednoduché dotazníkové nástroje založené na přítomnosti typických popisných charakteristik (tzv. deskriptorů). Cíle: Cílem studie byla validace českých jazykových verzí dvou nejčastěji užívaných jednoduchých screeningových dotazníkových nástrojů zaměřených na neexpertní diagnostiku neuropatické bolesti, tj. dotazníků DN4cz (Douleur Neuropathique en 4 Questions) a PDQcz (painDetect). Soubor a metodika: Po jazykové validaci českých verzí obou dotazníků byly tyto následně administrovány skupině pacientů s periferní neuropatickou bolestí při polyneuropatii diabetické či jiné etiologie (n = 65) a skupině nemocných s nociceptivní bolestí v důsledku pokročilé artrózy kyčelního nebo kolenního kloubu nebo chronických vertebrogenních potíží (n = 74). Výsledky: Oba dotazníky prokázaly vynikající srozumitelnost a snadnou použitelnost. Pacienti s neuropatickou bolestí dosahovali významně vyšších dílčích i celkových skóre obou dotazníků ve srovnání s pacienty s bolestí nociceptivní. ROC analýza potvrdila vynikající diagnostickou validitu obou dotazníků v odlišení neuropatické a nociceptivní bolesti. Dotazník PDQcz však dosahoval významně lepší diagnostické validity při nižším než doporučeném cut-off. Závěr: České verze dotazníků DN4 a PDQ prokázaly vynikající diagnostickou validitu v odlišení neuropatické a nociceptivní bolesti a lze je doporučit pro neexpertní diagnostiku neuropatické bolesti. Diagnostická validita dotazníku PDQ je vyšší při použití nižšího cut-off.
Background: Neuropathic pain is a frequent vlinical manifestation of many neurological disorders. Simple questionnaires mainly based on the presence of so called “neuropathic pain descriptors” represent the most important screening tool in the diagnosis of this condition. Aim: The aim of this study was to validate the Czech language version of two most frequently used questionnaires focused on neuropathic pain diagnosis by non-specialists, i.e., Douleur Neuropathique en 4 Questions (DN4cz) and painDetect (PDQcz). Patients and methods: Initially, the language validation of both questionnaires was performed. In the next step, two groups of patients were examined using these Czech language versions of both questionnaires: a group of patients suffering from peripheral neuropathic pain (in diabetic polyneuropathy or polyneuropathies of other etiology) (N = 65), and a group of individuals with nociceptive pain due to severe coxarthrosis or gonarthrosis or chronic low back pain (N = 74). Results: Both questionnaires proved to be easy-to-use and understandable. The patients with neuropathic pain reached significantly higher both partial and overall scores in both questionnaires compared to nociceptive pain patients. ROC analysis confirmed an excellent diagnostic validity of both questionnaires in the discrimination between neuropathic and nociceptive pain. However, the optimal cut-off with the highest possible diagnostic validity for the PDQcz was found significantly lower than had been recommended. Conclusions: The Czech language versions of both DN4 and PDQ questionnaires proved excellent diagnostic validity in the discrimination of neuropathic and nociceptive pain. Both of them thus can be recommended as easy and useful tools for diagnosis of neuropathic pain by non-specialists. To reach optimal diagnostic validity, the cut-off of the PDQ should be set lower than had been previously recommended.
- MeSH
- Diabetic Neuropathies diagnosis MeSH
- Humans MeSH
- Pain Measurement * methods MeSH
- Neuralgia * diagnosis MeSH
- Nociceptive Pain * diagnosis MeSH
- Polyneuropathies diagnosis MeSH
- Surveys and Questionnaires MeSH
- Reproducibility of Results MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Neuropatie (poškodenia periférnych nervov) delíme na mononeuropatie (postihnutie jedného periférneho nervu) a polyneuropatie (dva a viac postihnutých nervov), často označované jednoducho ako neuropatie. Príčinami mononeuropatií u detí sú hlavne úrazy. Pri polyneuropatiách sú príčiny hlavne hereditárne, nasledujú imunitne mediované neuropatie (dysimunitné/autoimunitné), neuropatie pri akútne prebiehajúcich infekciách, toxické (najčastejšie pri onkologickej liečbe), malnutričné a metabolické. Aj napriek tomu, že získané neuropatie u detí sú pomerne vzácne, poškodenie sa stáva ireverzibilné a mutilujúce pri mylnej diagnóze. Len skorá diagnostika a liečba dokáže tento priebeh zvrátiť.
Neuropathy (peripheral nerve damage) is divided into mononeuropathy (involvement of one peripheral nerves) and polyneuropathy (two or more affected nerves) often referred to simply as neuropathy. The main causes of mononeuropathy in children are injuries. In polyneuropathies, the causes are mainly hereditary, followed by immune-mediated neuropathies (dysimmune/autoimmune), neuropathies in acute infections, toxic (most often in cancer treatment), malnutrition and metabolism. Although acquired neuropathies in children are relatively rare, the damage becomes irreversible and mutilating at a misdiagnosis. Only early diagnosis and treatment can reverse this process.
- MeSH
- Diabetic Neuropathies etiology physiopathology MeSH
- Child MeSH
- Humans MeSH
- Polyneuropathies etiology physiopathology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
- Keywords
- nusinersen,
- MeSH
- Heredodegenerative Disorders, Nervous System * diagnosis genetics therapy MeSH
- Diagnosis, Differential MeSH
- Humans MeSH
- Peripheral Nervous System Diseases diagnosis etiology therapy MeSH
- Neurologic Examination methods MeSH
- Oligonucleotides administration & dosage therapeutic use MeSH
- Muscular Atrophy, Spinal diagnosis genetics therapy MeSH
- Spinocerebellar Ataxias diagnosis genetics therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
