in-vivo-electrophysiological-measurement-rat-ulnar-nerve-with-axonal

<em>In Vivo </em>Electrophysiological Measurement of the Rat Ulnar Nerve with Axonal Excitability Testing

Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and ...

University of New South Wales

&#x82E5;&#x8981;&#x8BC4;&#x4F30;&#x7CD6;&#x5C3F;&#x75C5;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x7684;&#x53D1;&#x5C55;&#xFF0C;&#x76EE;&#x524D;&#x7684;&#x7814;&#x7A76;&#xFF0C;&#x5BA1;&#x67E5;&#x4E86;&#x5468;&#x56F4;&#x5F25;&#x6F2B;&#x6027;&#x8F74;&#x7D22;&#x529F;&#x80FD;&#x53D8;&#x5316;&#x3002;&#x5728; 108 2 &#x578B;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005;&#x795E;&#x7ECF;&#x4F20;&#x5BFC;&#x7814;&#x7A76; &#xFF08;NCS&#xFF09;&#x3001; HbA(1c) &#x7EA7;&#x522B;&#x548C;&#x603B;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x5F97;&#x5206;&#x8FDB;&#x884C;&#x4E86;&#x795E;&#x7ECF;&#x5174;&#x594B;&#x6027;&#x6280;&#x672F; (TNS)&#x3002;&#x75C5;&#x4EBA;&#x88AB;&#x5206;&#x4E3A;&#x4E24;&#x4E2A;&#x7EC4;&#x7FA4;&#xFF1A; &#x65E0;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x7684;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005; (&#x4E0B;&#x7EC4; [n = 56]) &#x548C;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x7684;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005; (DN &#x7EC4; [n = 52]) &#x548C;&#x8FDB;&#x4E00;&#x6B65;&#x5230;&#x4E25;&#x91CD;&#x6027;&#x7B49;&#x7EA7; 0 (TNS 0-1 [n = 35])&#xFF0C;&#x7B49;&#x7EA7; 1 (TNS 2-8 [n = 42]&#xFF09;&#xFF0C;&#x548C; 2/3 &#x7EA7; (TNS 9-24 [n = 31])&#x3002;&#x7ED3;&#x679C;&#x663E;&#x793A;&#x4E0B;&#x7EC4;&#x5728;&#x5174;&#x594B;&#x6027;&#x53C2;&#x6570;&#x4E0E;&#x5E74;&#x9F84;&#x5339;&#x914D;&#x7684;&#x5BF9;&#x7167;&#x7EC4;&#x76F8;&#x6BD4;&#x6709;&#x5927;&#x5E45;&#x589E;&#x52A0;&#x7684;&#x9608;&#x503C;&#x3001; &#x957F;&#x65F6;&#x95F4;&#x7684;&#x5EF6;&#x8FDF;&#x548C;&#x66F4;&#x6539;&#x3002;&#x795E;&#x7ECF;&#x75C5;&#x60A3;&#x8005;&#x8868;&#x73B0;&#x51FA;&#x590D;&#x82CF;&#x5468;&#x671F;&#x53C2;&#x6570;&#x548C;&#x9664;&#x9608;&#x503C; electrotonus &#x7684;&#x91CD;&#x5927;&#x53D8;&#x5316;&#x3002;&#x4E0B;&#x7EC4;&#x7FA4;&#x5185;, &#x6709;&#x663E;&#x8457;&#x76F8;&#x5173;&#x6027; HbA(1c) &#x7EA7;&#x522B;&#x548C;&#x5EF6;&#x8FDF;&#x548C; subexcitability&#xFF0C;&#x800C;&#x4E0E;&#x795E;&#x7ECF;&#x75C5;&#x60A3;&#x8005; superexcitability &#x4F30;&#x8BA1;&#x80BE;&#x5C0F;&#x7403;&#x6EE4;&#x8FC7;&#x7387;&#x76F8;&#x5173;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x5174;&#x594B;&#x6027;&#x53C2;&#x6570;&#x6210;&#x4E3A;&#x9010;&#x6B65;&#x589E;&#x52A0;&#x4E34;&#x5E8A;&#x4E25;&#x91CD;&#x6027;&#x66F4;&#x5F02;&#x5E38;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x8C31;&#x7684;&#x5174;&#x594B;&#x6027;&#x5F02;&#x5E38;&#x7684;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005;&#x548C;&#x65E9;&#x671F;&#x5F25;&#x6F2B;&#x6027;&#x8F74;&#x7D22;&#x529F;&#x80FD;&#x969C;&#x788D;&#x6709;&#x5173;&#xFF0C;&#x53EF;&#x80FD;&#x4F1A;&#x68C0;&#x6D4B;&#x4E4B;&#x524D;&#x53D1;&#x5C55;&#x7684;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x3002;&#x4F5C;&#x4E3A;&#x5174;&#x594B;&#x6027;&#x53C2;&#x6570;&#x9010;&#x6B65;&#x53D8;&#x5316;&#x76F8;&#x5173;&#x75C5;&#x53D8;&#x7684;&#x4E25;&#x91CD;&#x6027;&#xFF0C;&#x5174;&#x594B;&#x6027;&#x6D4B;&#x8BD5;&#x53EF;&#x80FD;&#x63D0;&#x4F9B;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x7684;&#x65E9;&#x671F;&#x53D1;&#x5C55;&#x548C;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x7684;&#x7CD6;&#x5C3F;&#x75C5;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#xFF0C;&#x63D0;&#x4F9B;&#x6DF1;&#x5165;&#x4E86;&#x89E3;&#x751F;&#x4EA7;&#x6027;&#x8F74;&#x7A81;&#x529F;&#x80FD;&#x969C;&#x788D;&#x7684;&#x75C5;&#x7406;&#x751F;&#x7406;&#x673A;&#x5236;&#x3002;

&#x9010;&#x6E10;&#x5F25;&#x6F2B;&#x6027;&#x8F74;&#x7D22;&#x529F;&#x80FD;&#x969C;&#x788D;&#x4E4B;&#x524D;&#x5728; 2 &#x578B;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005;&#x4E2D;&#x795E;&#x7ECF;&#x75C5;&#x53D8;&#x7684;&#x53D1;&#x5C55;&#x3002;

To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0-1 [n = 35]), grade 1 (TNS 2-8 [n = 42]), and grade 2/3 (TNS 9-24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.

Progressive Axonal Dysfunction Precedes Development of Neuropathy in Type 2 Diabetes.

Pour &eacute;valuer le d&eacute;veloppement de la neuropathie diab&eacute;tique, la pr&eacute;sente &eacute;tude a examin&eacute; les changements dans la fonction axonale p&eacute;riph&eacute;rique. Techniques d&#39;excitabilit&eacute; nerveuse ont &eacute;t&eacute; entrepris en 108 patients diab&eacute;tiques de type 2 avec &eacute;tudes de conduction de nerf (NCS), niveaux de HbA(1c) et le total de la neuropathie (TNS). Les patients ont &eacute;t&eacute; class&eacute;s en deux cohortes : patients diab&eacute;tiques sans neuropathie (groupe DWN [n = 56]) et les patients diab&eacute;tiques avec neuropathie (groupe DN [n = 52]) et plus loin dans la s&eacute;v&eacute;rit&eacute; de grade 0 (AMT 0-1 [n = 35]), classe 1 (AMT 2-8 [n = 42]) et 2e/3e ann&eacute;e (AMT 9-24 [n = 31]). Les r&eacute;sultats ont r&eacute;v&eacute;l&eacute; que le groupe de la DWN &eacute;tait un seuil significativement accru, temps de latence prolong&eacute;e et des changements dans les param&egrave;tres de l&#39;excitabilit&eacute; par rapport aux sujets t&eacute;moins appari&eacute;s selon l&#39;&acirc;ge. Les patients atteints de neuropathie a d&eacute;montr&eacute; une alt&eacute;ration significative dans les param&egrave;tres du cycle de r&eacute;cup&eacute;ration et d&#39;electrotonus de seuil d&eacute;polarisation. Au sein de la cohorte de la DWN, il y avait des corr&eacute;lations significatives entre le niveau de HbA(1c) et de latence et de subexcitability, tandis que le taux de filtration glom&eacute;rulaire estim&eacute; corr&eacute;l&eacute; avec superexcitability chez les patients atteints de neuropathie. En outre, param&egrave;tres de l&#39;excitabilit&eacute; est devenue progressivement plus anormales avec une augmentation de la s&eacute;v&eacute;rit&eacute; clinique. Ces r&eacute;sultats sugg&egrave;rent un spectre d&#39;anomalies d&#39;excitabilit&eacute; chez les patients diab&eacute;tiques et ce dysfonctionnement axonal pr&eacute;coce peut &ecirc;tre d&eacute;tect&eacute; avant l&#39;apparition de la neuropathie. Des changements progressifs dans les param&egrave;tres de l&#39;excitabilit&eacute; corr&eacute;l&eacute;es &agrave; la s&eacute;v&eacute;rit&eacute; de la neuropathie, test d&#39;excitabilit&eacute; peut-&ecirc;tre pr&eacute;voir un biomarqueur du d&eacute;veloppement pr&eacute;coce et la gravit&eacute; de la neuropathie diab&eacute;tique, pour mieux comprendre les m&eacute;canismes physiopathologiques produisant la dysfonction axonale.

Un dysfonctionnement progressif Axonal pr&eacute;c&egrave;de le d&eacute;veloppement de la neuropathie dans le diab&egrave;te de Type 2.

Um die Entwicklung der diabetischen Neuropathie zu bewerten, untersucht die aktuelle Studie &Auml;nderungen in peripheren axonalen Funktion. Nerv Erregbarkeit Techniken wurden durchgef&uuml;hrt in 108 Typ 2-Diabetikern mit Nerv &Uuml;bertragung Studien (NCS), HbA(1c) Ebenen und insgesamt Neuropathie Partitur (TNS). Patienten wurden in zwei Kohorten kategorisiert: Patienten mit Diabetes ohne Neuropathie (DWN-Gruppe [n = 56]) und Patienten mit Diabetes mellitus mit Neuropathie (DN-Gruppe [n = 52]) und weiter in schwere Grad 0 (TNS 0-1 [n = 35]), Klasse 1 (TNS 2-8 [n = 42]), und Klasse 2/3 (TNS-9-24 [n = 31]). Ergebnisse ergab, dass die DWN-Gruppe eine deutlich h&ouml;here Schwelle, verl&auml;ngerte Latenz und &Auml;nderungen in Erregbarkeit Parameter mit altersbezogenen Kontrollpersonen verglichen hatte. Patienten mit Neuropathie zeigten signifikante &Auml;nderung der Wiederaufnahme Zyklus Parameter und depolarisierende Schwellenwert Electrotonus. Innerhalb der DWN-Kohorte gab es signifikante Korrelationen zwischen HbA(1c) und Latenz und Subexcitability, w&auml;hrend die gesch&auml;tzte Glomerul&auml;re Filtrationsrate mit Superexcitability bei Patienten mit Neuropathie korreliert. Dar&uuml;ber hinaus wurde die Erregbarkeit Parameter schrittweise mehr abnorme mit zunehmender klinischen Schweregrad. Diese Resultate schlagen ein Spektrum von Anomalien der Erregbarkeit bei Patienten mit Diabetes und die fr&uuml;hen axonale Dysfunktion kann vor der Entwicklung der Neuropathie erkannt werden. Da progressive Ver&auml;nderungen Erregbarkeit Parameter zu Neuropathie Schweregrad korreliert, vorsehen Erregbarkeit testen Biomarker der fr&uuml;hen Entwicklung und schwere Diabetische Neuropathie, bietet Einblicke in die pathophysiologischen Mechanismen, die produzieren axonale Dysfunktion.

Progressive axonale Dysfunktion vorausgeht Entwicklung der Neuropathie bei Typ 2 Diabetes.

Per valutare lo sviluppo di neuropatia diabetica, l&#39;attuale studio esaminato cambiamenti nella funzione assonale periferico. Tecniche di eccitabilit&agrave; nervosa sono stati intrapresi in 108 pazienti diabetici di tipo 2 con studio della conduzione nervosa (NCS), i livelli di HbA(1c) e punteggio totale neuropatia (TNS). I pazienti sono stati suddivisi in due coorti: i pazienti con diabete senza neuropatia (gruppo DWN [n = 56]) e i pazienti con diabete con neuropatia (gruppo DN [n = 52]) e ulteriormente in gravit&agrave; di grado 0 (TNS 0-1 [n = 35]), grado 1 (TNS 2-8 [n = 42]) e grado 2/3 (TNS 9-24 [n = 31]). Risultati hanno rivelato che il gruppo DWN aveva una soglia significativamente aumentata, prolungata latenza e cambiamenti nei parametri di eccitabilit&agrave; rispetto ai soggetti di controllo di et&agrave; corrispondente. I pazienti con neuropatia dimostrato alterazione significativa nei parametri del ciclo di recupero e depolarizing electrotonus soglia. All&#39;interno della coorte DWN, c&#39;erano significative correlazioni tra livello di HbA(1c) e latenza e subexcitability, mentre il tasso di filtrazione glomerulare stimata correlato con superexcitability nei pazienti con neuropatia. Inoltre, i parametri dell&#39;eccitabilit&agrave; &egrave; diventato progressivamente pi&ugrave; anormali con sempre maggiore gravit&agrave; clinica. Questi risultati suggeriscono un spettro di anomalie eccitabilit&agrave; nei pazienti con diabete e che la disfunzione assonale precoce pu&ograve; essere rilevata prima dello sviluppo di neuropatia. Come progressivi cambiamenti nei parametri di eccitabilit&agrave; correlata alla gravit&agrave; della neuropatia, eccitabilit&agrave; test pu&ograve; fornire un biomarker dello sviluppo precoce e la gravit&agrave; della neuropatia diabetica, fornendo approfondimenti sui meccanismi fisiopatologici producendo disfunzione assonale.

Progressiva disfunzione assonale precede lo sviluppo della neuropatia in diabete di tipo 2.

&#x7CD6;&#x5C3F;&#x75C5;&#x6027;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30D1;&#x30C1;&#x30FC;&#x306E;&#x958B;&#x767A;&#x3092;&#x8A55;&#x4FA1;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;&#x73FE;&#x5728;&#x306E;&#x7814;&#x7A76;&#x3067;&#x306F;&#x672B;&#x68A2;&#x306E;&#x8EF8;&#x7D22;&#x6A5F;&#x80FD;&#x306E;&#x5909;&#x5316;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x795E;&#x7D4C;&#x4F1D;&#x5C0E;&#x691C;&#x67FB; (NCS)&#x3001;HbA(1c) &#x30EC;&#x30D9;&#x30EB;&#x3001;&#x304A;&#x3088;&#x3073;&#x5408;&#x8A08;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30D1;&#x30B7;&#x30FC; &#x30B9;&#x30B3;&#x30A2;&#x3068; 108 2 &#x578B;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005;&#x306B;&#x304A;&#x3051;&#x308B;&#x795E;&#x7D4C;&#x8208;&#x596E;&#x6027;&#x30C6;&#x30AF;&#x30CB;&#x30C3;&#x30AF;&#x306B;&#x56FD;&#x5185; (TNS)&#x3002;&#x60A3;&#x8005;&#x306F;&#x3001;2 &#x3064;&#x306E;&#x30B3;&#x30DB;&#x30FC;&#x30C8;&#x306B;&#x5206;&#x985E;&#x3055;&#x308C;&#x305F;: &#x7CD6;&#x5C3F;&#x75C5;&#x6027;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x60A3;&#x8005; (DWN &#x30B0;&#x30EB;&#x30FC;&#x30D7; [n = 56]) &#x3068;&#x7CD6;&#x5C3F;&#x75C5;&#x6027;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x306F;&#x60A3;&#x8005; (DN &#x30B0;&#x30EB;&#x30FC;&#x30D7; [n = 52])&#x3001;&#x3055;&#x3089;&#x306B;&#x30B0;&#x30EC;&#x30FC;&#x30C9;&#x306E;&#x91CD;&#x5927;&#x5EA6;&#x306B; 0 (TNS 0 1 [n = 35])&#x3001;&#x30B0;&#x30EC;&#x30FC;&#x30C9; 1 (TNS 2-8 [n = 42]&#xFF09; &#x3068;&#x30B0;&#x30EC;&#x30FC;&#x30C9; 2/3 (TNS 9 24 [n = 31])&#x3002;&#x7D50;&#x679C; DWN &#x30B0;&#x30EB;&#x30FC;&#x30D7;&#x304C;&#x5927;&#x5E45;&#x306B;&#x5897;&#x52A0;&#x3057;&#x305F;&#x3057;&#x304D;&#x3044;&#x5024;&#x3001;&#x9577;&#x6642;&#x9593;&#x306E;&#x9045;&#x5EF6;&#x3001;&#x304A;&#x3088;&#x3073;&#x5909;&#x66F4;&#x306E;&#x5E74;&#x9F62;&#x3092;&#x30DE;&#x30C3;&#x30C1;&#x3055;&#x305B;&#x305F;&#x5BFE;&#x7167;&#x88AB;&#x9A13;&#x8005;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x8208;&#x596E;&#x6027;&#x30D1;&#x30E9;&#x30E1;&#x30FC;&#x30BF;&#x30FC;&#x3067;&#x3042;&#x3063;&#x305F;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30D1;&#x30C1;&#x30FC;&#x60A3;&#x8005;&#x56DE;&#x5FA9;&#x30B5;&#x30A4;&#x30AF;&#x30EB; &#x30D1;&#x30E9;&#x30E1;&#x30FC;&#x30BF;&#x30FC;&#x3068;&#x5206;&#x6975;&#x306E;&#x3057;&#x304D;&#x3044;&#x5024; electrotonus &#x306B;&#x91CD;&#x8981;&#x306A;&#x5909;&#x66F4;&#x3092;&#x793A;&#x3057;&#x305F;&#x3002;DWN &#x30B3;&#x30DB;&#x30FC;&#x30C8;&#x5185;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x60A3;&#x8005;&#x306B;&#x304A;&#x3051;&#x308B; superexcitability &#x63A8;&#x5B9A;&#x7CF8;&#x7403;&#x4F53;&#x6FFE;&#x904E;&#x7387;&#x76F8;&#x95A2;&#x306B;&#x5BFE;&#x3057; HbA(1c) &#x30EC;&#x30D9;&#x30EB;&#x3068;&#x9045;&#x5EF6;&#x3068; subexcitability &#x3068;&#x6709;&#x610F;&#x306A;&#x76F8;&#x95A2;&#x304C;&#x3042;&#x3063;&#x305F;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x8208;&#x596E;&#x6027;&#x30D1;&#x30E9;&#x30E1;&#x30FC;&#x30BF;&#x30FC;&#x306F;&#x81E8;&#x5E8A;&#x7684;&#x91CD;&#x75C7;&#x5EA6;&#x306E;&#x5897;&#x52A0;&#x3068;&#x3068;&#x3082;&#x306B;&#x5F90;&#x3005; &#x306B;&#x3088;&#x308A;&#x7570;&#x5E38;&#x306B;&#x306A;&#x3063;&#x305F;&#x3002;&#x793A;&#x5506;&#x3055;&#x308C;&#x305F;&#x7CD6;&#x5C3F;&#x75C5;&#x60A3;&#x8005;&#x306B;&#x304A;&#x3051;&#x308B;&#x8208;&#x596E;&#x6027;&#x7570;&#x5E38;&#x306E;&#x30B9;&#x30DA;&#x30AF;&#x30C8;&#x30EB;&#x3068;&#x305D;&#x306E;&#x521D;&#x671F;&#x8EF8;&#x7D22;&#x969C;&#x5BB3;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x306E;&#x958B;&#x767A;&#x524D;&#x306B;&#x691C;&#x51FA;&#x3053;&#x3068;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x8208;&#x596E;&#x6027;&#x30D1;&#x30E9;&#x30E1;&#x30FC;&#x30BF;&#x30FC;&#x306E;&#x9032;&#x6B69;&#x7684;&#x306A;&#x5909;&#x5316;&#x3092;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x306E;&#x91CD;&#x75C7;&#x5EA6;&#x306B;&#x76F8;&#x95A2;&#x306E;&#x3088;&#x3046;&#x306B;&#x3001;&#x8208;&#x596E;&#x6027;&#x306E;&#x30C6;&#x30B9;&#x30C8;&#x306E;&#x65E9;&#x671F;&#x958B;&#x767A;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3068;&#x8EF8;&#x7D22;&#x306E;&#x6A5F;&#x80FD;&#x4E0D;&#x5168;&#x306E;&#x751F;&#x6210;&#x75C5;&#x614B;&#x751F;&#x7406;&#x5B66;&#x7684;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306B;&#x6D1E;&#x5BDF;&#x529B;&#x3092;&#x63D0;&#x4F9B;&#x3059;&#x308B;&#x3001;&#x7CD6;&#x5C3F;&#x75C5;&#x6027;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x306E;&#x91CD;&#x5927;&#x5EA6;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x9032;&#x6B69;&#x7684;&#x306A;&#x8EF8;&#x7D22;&#x969C;&#x5BB3;&#x30BF;&#x30A4;&#x30D7; 2 &#x306E;&#x7CD6;&#x5C3F;&#x75C5;&#x306E;&#x795E;&#x7D4C;&#x969C;&#x5BB3;&#x306E;&#x958B;&#x767A;&#x306B;&#x5148;&#x884C;&#x3057;&#x307E;&#x3059;&#x3002;

&#xB2F9;&#xB1E8;&#xBCD1; &#xC2E0;&#xACBD; &#xBCD1;&#xC758; &#xBC1C;&#xC804;&#xC744; &#xD3C9;&#xAC00; &#xD558; &#xD604;&#xC7AC; &#xC5F0;&#xAD6C; &#xC8FC;&#xBCC0; axonal &#xAE30;&#xB2A5;&#xC5D0; &#xBCC0;&#xD654;&#xB97C; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xC2E0;&#xACBD; &#xD765;&#xBD84; &#xAE30;&#xBC95; &#xC2E0;&#xACBD; &#xC804;&#xB3C4; &#xC5F0;&#xAD6C; (NCS), HbA(1c) &#xC218;&#xC900; &#xBC0F; &#xCD1D; &#xC2E0;&#xACBD; &#xC7A5;&#xC560; &#xC810;&#xC218;&#xC640; 108 2 &#xD615; &#xB2F9;&#xB1E8;&#xBCD1; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC2DC;&#xD589; &#xB41C; &#xD588;&#xB2E4; (TNS). &#xD658;&#xC790; &#xB450; &#xBB34;&#xB9AC;&#xB85C; &#xBD84;&#xB958; &#xD588;&#xB2E4;: &#xC2E0;&#xACBD; &#xC7A5; &#xD574; &#xC5C6;&#xC774; &#xB2F9;&#xB1E8;&#xBCD1; &#xD658;&#xC790; (DWN &#xADF8;&#xB8F9; [n = 56]) &#xC2E0;&#xACBD; &#xC7A5; &#xD574; &#xB2F9;&#xB1E8;&#xBCD1; &#xD658;&#xC790; (DN &#xADF8;&#xB8F9; [n = 52]) &#xB354; &#xC2EC;&#xAC01;&#xB3C4;&#xC5D0; 0 &#xD559;&#xB144; (TNS 0-1 [n = 35]), 1 &#xD559;&#xB144; (TNS 2-8 [n = 42]), &#xBC0F; 2/3 &#xD559;&#xB144; (TNS 9-24 [n 31 =]). &#xACB0;&#xACFC; &#xACF5;&#xAC1C; DWN &#xADF8;&#xB8F9; &#xD06C;&#xAC8C; &#xC99D;&#xAC00; &#xC784;&#xACC4;&#xAC12;, &#xC7A5;&#xAE30;&#xAC04;&#xB41C; &#xB300;&#xAE30; &#xC2DC;&#xAC04; &#xBC0F; &#xBCC0;&#xACBD; &#xD765;&#xBD84; &#xB9E4;&#xAC1C; &#xBCC0;&#xC218;&#xC5D0; &#xC77C;&#xCE58; &#xD558;&#xB294; &#xB098;&#xC774; &#xC81C;&#xC5B4; &#xACFC;&#xBAA9;&#xC5D0; &#xBE44;&#xD574; &#xD588;&#xB2E4;. &#xC2E0;&#xACBD; &#xBCD1; &#xD658;&#xC790; &#xBCF5;&#xAD6C; &#xC8FC;&#xAE30; &#xB9E4;&#xAC1C; &#xBCC0;&#xC218;&#xC640; depolarizing &#xC784;&#xACC4;&#xAC12; electrotonus&#xC5D0; &#xC0C1;&#xB2F9;&#xD55C; &#xBCC0;&#xD654;&#xB97C; &#xC124;&#xBA85; &#xD588;&#xB2E4;. DWN &#xCF54; &#xD638;&#xD2B8; &#xB0B4;&#xC5D0;&#xC11C; &#xCD94;&#xC815;&#xB41C; &#xC0AC; &#xC5EC;&#xACFC; &#xC18D;&#xB3C4; &#xC2E0;&#xACBD; &#xBCD1; &#xD658;&#xC790;&#xC5D0;&#xC11C; superexcitability&#xC640; &#xC0C1;&#xAD00; &#xD558;&#xB294; &#xBC18;&#xBA74; HbA(1c) &#xC218;&#xC900; &#xBC0F; &#xB300;&#xAE30; &#xC2DC;&#xAC04; &#xBC0F; subexcitability, &#xC0AC;&#xC774;&#xC758; &#xC911;&#xC694; &#xD55C; &#xC0C1;&#xAD00; &#xAD00;&#xACC4; &#xD588;&#xB2E4;. &#xB610;&#xD55C;, &#xD765;&#xBD84; &#xB9E4;&#xAC1C; &#xBCC0;&#xC218; &#xC784;&#xC0C1; &#xC2EC;&#xAC01;&#xB3C4; &#xC99D;&#xAC00; &#xD568;&#xAED8; &#xC810;&#xC9C4;&#xC801;&#xC73C;&#xB85C; &#xB354; &#xC774;&#xC0C1; &#xB418;&#xC5C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xB2F9;&#xB1E8;&#xBCD1; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC774;&#xC0C1; &#xD765;&#xBD84;&#xC758; &#xC2A4;&#xD399;&#xD2B8;&#xB7FC;&#xC744; &#xC81C;&#xC548; &#xD558; &#xACE0; &#xADF8; &#xCD08;&#xAE30; axonal &#xBD80;&#xC804; &#xC2E0;&#xACBD; &#xBCD1;&#xC758; &#xAC1C;&#xBC1C; &#xC774;&#xC804;&#xC5D0; &#xAC80;&#xC0C9; &#xB420; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC73C;&#xB85C; &#xD765;&#xBD84; &#xB9E4;&#xAC1C; &#xBCC0;&#xC218;&#xC5D0;&#xC11C; &#xC9C4;&#xBCF4;&#xC801;&#xC778; &#xBCC0;&#xD654; &#xC2E0;&#xACBD; &#xBCD1; &#xC2EC;&#xAC01;&#xB3C4;&#xC5D0; &#xC0C1;&#xAD00;, &#xD765;&#xBD84; &#xD14C;&#xC2A4;&#xD2B8; &#xCD08;&#xAE30; &#xAC1C;&#xBC1C;&#xC758; biomarker &#xBC0F; axonal &#xBD80;&#xC804; &#xC0DD;&#xC0B0; pathophysiological &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC5D0; &#xB300; &#xD55C; &#xD1B5;&#xCC30;&#xB825;&#xC744; &#xC81C;&#xACF5; &#xD558; &#xACE0; &#xB2F9;&#xB1E8;&#xBCD1; &#xC2E0;&#xACBD; &#xBCD1;&#xC758; &#xC2EC;&#xAC01;&#xB3C4; &#xC81C;&#xACF5;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC9C4;&#xBCF4;&#xC801;&#xC778; Axonal &#xBD80;&#xC804; &#xD0C0;&#xC785;-2 &#xB2F9;&#xB1E8;&#xBCD1;&#xC5D0;&#xC11C; &#xC2E0;&#xACBD; &#xC7A5; &#xD574;&#xC758; &#xAC1C;&#xBC1C;&#xC744; &#xC55E;.

Para evaluar el desarrollo de la neuropat&iacute;a diab&eacute;tica, el presente estudio examina cambios en la funci&oacute;n axonal perif&eacute;rica. T&eacute;cnicas de excitabilidad del nervio se llevaron a cabo en 108 pacientes diab&eacute;ticos tipo 2 con estudios de conducci&oacute;n nerviosa (NCS), buenn y puntuaci&oacute;n total de la neuropat&iacute;a (TNS). Pacientes se categorizaron en dos cohortes: pacientes con diabetes sin neuropat&iacute;a (Grupo DWN [n = 56]) y en pacientes diab&eacute;ticos con neuropat&iacute;a (Grupo DN [n = 52]) y a&uacute;n m&aacute;s en la severidad del grado 0 (TNS 0-1 [n = 35]), grado 1 (TNS 2-8 [n = 42]) y grado 2/3 (TNS 9-24 [n = 31]). Los resultados revelaron que el grupo de las DWN ten&iacute;a un umbral significativamente mayor latencia prolongada y cambios en los par&aacute;metros de la excitabilidad en comparaci&oacute;n con sujetos de edad comparable del control. Los pacientes con neuropat&iacute;a demostraron alteraci&oacute;n significativa en los par&aacute;metros del ciclo de recuperaci&oacute;n y electrotonus de despolarizaci&oacute;n umbral. Dentro de la cohorte de las DWN, hubo correlaciones significativas entre el nivel de buenn y latencia y subexcitability, mientras que la tasa de filtraci&oacute;n glomerular estimada correlacionados con superexcitability en pacientes con neuropat&iacute;a. Adem&aacute;s, par&aacute;metros de excitabilidad se convirtieron progresivamente m&aacute;s anormales con el aumento de la severidad cl&iacute;nica. Estos resultados sugieren un espectro de anormalidades de la excitabilidad en pacientes con diabetes y esa disfunci&oacute;n axonal temprana puede detectarse antes del desarrollo de la neuropat&iacute;a. Como cambios progresivos en los par&aacute;metros de la excitabilidad correlacionan con la severidad de la neuropat&iacute;a, excitabilidad pruebas pueden proporcionar un biomarcador del desarrollo temprano y la severidad de la neuropat&iacute;a diab&eacute;tica, proporcionando informaci&oacute;n sobre los mecanismos fisiopatol&oacute;gicos que produce disfunci&oacute;n axonal.

Disfunci&oacute;n Axonal progresiva precede el desarrollo de la neuropat&iacute;a en la Diabetes tipo 2.

The present study was undertaken to determine whether there were changes evident in axonal membrane function prior to the onset of neuropathy in patients with type 1 and type 2 diabetes.

Axonal dysfunction prior to neuropathy onset in type 1 diabetes.

Pharmacological agents for diabetic peripheral neuropathy (DN) target a number of mechanisms, including sodium channel function and γ-aminobutyric acid-minergic processes. At present, prescription is undertaken on a trial-and-error basis, leading to prolonged medication trials and greater healthcare costs. Nerve-excitability techniques are a novel method of assessing axonal ion channel function in the clinical setting. The aim of this study was to determine the effects of axonal ion channel dysfunction on neuropathy-specific quality-of-life (QoL) measures in DN.

Effects of axonal ion channel dysfunction on quality of life in type 2 diabetes.

Peripheral neuropathy is the most common neurological complication in end-stage kidney disease. While high flux hemodialysis (HFHD) and hemodiafiltration (HDF) have become the preferred options for extracorporeal dialysis therapy, the effects of these treatments on nerve excitability have not yet been examined.

Effects of hemodiafiltration and high flux hemodialysis on nerve excitability in end-stage kidney disease.

The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition.

Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies.

Potassium (K(+)) has been implicated as a factor in the development of uraemic neuropathy. This study was undertaken to investigate whether hyperkalaemia plays a causal role in axonal dysfunction in end-stage kidney disease (ESKD).

Evidence for a causal relationship between hyperkalaemia and axonal dysfunction in end-stage kidney disease.

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown.

Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus.

There is no specific treatment for neuropathy in chronic kidney disease (CKD). We compared nerve function across hemodialysis (HD) and peritoneal dialysis (PD).

Comparative study to evaluate the effects of peritoneal and hemodialysis on peripheral nerve function.

Diabetic neuropathy is a debilitating complication of diabetes. Animal models of type 1 diabetes (T1DM) suggest that functional and structural changes, specifically axo-glial dysjunction, may contribute to neuropathy development. The present study sought to examine and characterise early sensory axonal function in T1DM patients in the absence of clinical neuropathy.

In vivo evidence of reduced nodal and paranodal conductances in type 1 diabetes.

Glycemic variability (GV) may be a novel factor in the pathogenesis of diabetic complications. However, the effect of GV on peripheral nerve function has not been explored systematically.

Association between glycemic variability and peripheral nerve dysfunction in type 1 diabetes.

We explored the nerve ultrasound (US) characteristics of 15 patients with end-stage kidney disease (ESKD) and correlated these findings with clinical severity and electrophysiological parameters of neuropathy.

Haemodialysis alters peripheral nerve morphology in end-stage kidney disease.

Nerve excitability testing by threshold-tracking is the only available method to study axonal ion channel function and membrane potential in the clinical setting. The measures are, however, indirect and the interpretation of neuropathic changes remains challenging. The same multiple measures of axonal excitability were adapted to further explore the pathophysiological changes in rodent disease models under pharmacologic and genetic manipulations. These studies are typically limited to the investigation of the "long nerves" such as the tail or the tibial nerves.

Nerve excitability in the rat forelimb: a technique to improve translational utility.

Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages.

Neurological complications in chronic kidney disease.

Diabetes may impair the capacity for neuroplasticity such that patients experience a slower and poorer recovery after stroke. The current study investigated changes in cortical function in stroke patients with diabetes to determine how this comorbidity may affect poststroke cortical plasticity and thereby functional recovery. From a cohort of 57 participants, threshold-tracking transcranial magnetic stimulation was used to assess cortical function over the ipsilateral and contralesional hemispheres in 7 patients with diabetes after an acute stroke compared with 12 stroke patients without diabetes. Cortical function was also assessed in 8 patients with diabetes without stroke and 30 normal control subjects. After acute stroke, short-interval intracortical inhibition (SICI) was reduced over both motor cortices in stroke patients without diabetes compared with normal control patients, while in stroke patients with diabetes, SICI was only reduced over the contralesional but not the ipsilesional cortex compared with control patients with diabetes. In addition, SICI was significantly reduced in the control patients with diabetes compared with normal control patients. These results have demonstrated the absence of ipsilesional cortical excitability change after diabetic strokes, suggesting impaired capacity for neuroplasticity over this hemisphere as a consequence of a "double-hit" phenomenon because of preexisting alterations in cortical function in nonstroke patients with diabetes. The reliance on reorganization over the contralesional cortex after stroke will likely exert influence on poststroke recovery in patients with diabetes.

The Effect of Diabetes on Cortical Function in Stroke: Implications for Poststroke Plasticity.

We quantified intraneural blood flow (INBF) in 18 patients with end-stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity, and nerve excitability parameters.

Article	Year
Progressive Axonal Dysfunction Precedes Development of Neuropathy in Type 2 Diabetes. Diabetes\| PubMed ID: 22522615	2012
Axonal dysfunction prior to neuropathy onset in type 1 diabetes. Diabetes/metabolism research and reviews\| PubMed ID: 23008000	2013
Effects of axonal ion channel dysfunction on quality of life in type 2 diabetes. Diabetes care\| PubMed ID: 23404298	2013
Effects of hemodiafiltration and high flux hemodialysis on nerve excitability in end-stage kidney disease. PloS one\| PubMed ID: 23536855	2013
Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 23683523	2013
Evidence for a causal relationship between hyperkalaemia and axonal dysfunction in end-stage kidney disease. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 23867066	2014
Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus. Diabetes/metabolism research and reviews\| PubMed ID: 25066412	2015
Comparative study to evaluate the effects of peritoneal and hemodialysis on peripheral nerve function. Muscle & nerve\| PubMed ID: 26660121	2016
In vivo evidence of reduced nodal and paranodal conductances in type 1 diabetes. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 26725257	2016
Association between glycemic variability and peripheral nerve dysfunction in type 1 diabetes. Muscle & nerve\| PubMed ID: 27465125	2016
Haemodialysis alters peripheral nerve morphology in end-stage kidney disease. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 27743880	2017
Nerve excitability in the rat forelimb: a technique to improve translational utility. Journal of neuroscience methods\| PubMed ID: 27771307	2017
Neurological complications in chronic kidney disease. JRSM cardiovascular disease\| PubMed ID: 27867500	2016
The Effect of Diabetes on Cortical Function in Stroke: Implications for Poststroke Plasticity. Diabetes\| PubMed ID: 28325854	2017
Effects of hemodialysis on intraneural blood flow in end-stage kidney disease. Muscle & nerve\| PubMed ID: 28556350	2018

Ria Arnold

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