Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis.

Rationale: The anatomical substrate of skeletal muscle autonomic innervation has remained underappreciated since it was described many decades ago. As such, the structural and functional features of muscle sympathetic innervation are largely undetermined in both physiology and pathology, mainly due to methodological limitations in the histopathological analysis of small neuronal fibers in tissue samples. Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease which mainly targets motor neurons, and despite autonomic symptoms occurring in a significant fraction of patients, peripheral sympathetic neurons (SNs) are generally considered unaffected and, as such, poorly studied. Purpose: In this research, we compared sympathetic innervation of normal and ALS muscles, through structural analysis of the sympathetic network in human and murine tissue samples. Methods and Results: We first refined tissue processing to circumvent methodological limitations interfering with the detection of muscle sympathetic innervation. The optimized "Neuro Detection Protocol" (NDP) was validated in human muscle biopsies, demonstrating that SNs innervate, at high density, both blood vessels and skeletal myofibers, independent of the fiber metabolic type. Subsequently, NDP was exploited to analyze sympathetic innervation in muscles of SOD1G93A mice, a preclinical ALS model. Our data show that ALS murine muscles display SN denervation, which has already initiated at the early disease stage and worsened during aging. SN degeneration was also observed in muscles of MLC/SOD1G93A mice, with muscle specific expression of the SOD1G93A mutant gene. Notably, similar alterations in SNs were observed in muscle biopsies from an ALS patient, carrying the SOD1G93A mutation. Conclusion: We set up a protocol for the analysis of murine and, more importantly, human muscle sympathetic innervation. Our results indicate that SNs are additional cell types compromised in ALS and suggest that dysfunctional SOD1G93A muscles affect their sympathetic innervation.

Anterior interosseous nerve: anatomical study and clinical implications / Nervo interósseo anterior: estudo anatômico e implicações clínicas

ABSTRACT Objective: The goal of this study was to describe anatomical variations and clinical implications of anterior interosseous nerve. In complete anterior interosseous nerve palsy, the patient is unable to flex the distal phalanx of the thumb and index finger; in incomplete anterior interosseous nerve palsy, there is less axonal damage, and either the thumb or the index finger are affected. Methods: This study was based on the dissection of 50 limbs of 25 cadavers, 22 were male and three, female. Age ranged from 28 to 77 years, 14 were white and 11 were non-white; 18 were prepared by intra-arterial injection of a solution of 10% glycerol and formaldehyde, and seven were freshly dissected cadavers. Results: The anterior interosseous nerve arose from the median nerve, an average of 5.2 cm distal to the intercondylar line. In 29 limbs, it originated from the nerve fascicles of the posterior region of the median nerve and in 21 limbs, of the posterolateral fascicles. In 41 limbs, the anterior interosseous nerve positioned between the humeral and ulnar head of the pronator teres muscle. In two limbs, anterior interosseous nerve duplication was observed. In all members, it was observed that the anterior interosseous nerve arose from the median nerve proximal to the arch of the flexor digitorum superficialis muscle. In 24 limbs, the branches of the anterior interosseous nerve occurred proximal to the arch and in 26, distal to it. Conclusion: The fibrous arches formed by the humeral and ulnar heads of the pronator teres muscle, the fibrous arch of the flexor digitorum superficialis muscle, and the Gantzer muscle (when hypertrophied and positioned anterior to the anterior interosseous nerve), can compress the nerve against deep structures, altering its normal course, by narrowing its space, causing alterations longus and flexor digitorum profundus muscles.

RESUMO Objetivo: Analisar as relações anatômicas e as variações do nervo interósseo anterior e suas implicações clínicas. A paralisia completa do nervo interósseo anterior resulta na incapacidade de fletir as falanges distal do polegar e indicador; na incompleta, ocorre menor dano axonal e apenas o polegar ou o indicador são afetados. Método: Este estudo baseou-se na dissecção de 50 membros de 25 cadáveres, 22 eram do sexo masculino e três do feminino. A idade variou entre 28 e 77 anos, 14 da etnia branca e 11 não branca; 18 foram preparados por injeção intra-arterial de uma solução de glicerina e formol a 10% e sete foram dissecados a fresco. Resultados: O nervo interósseo anterior originou-se do nervo mediano em média de 5,2 cm distal à linha intercondilar. Em 29 membros, originou-se dos fascículos nervosos da região posterior do nervo mediano e em 21 membros, dos fascículos posterolaterais. Em 41 membros, o nervo interósseo anterior posicionava-se entre as cabeças umeral e ulnar do músculo pronador redondo. Em dois membros, observou-se a duplicação do nervo interósseo anterior. Em todos os membros, registramos que o nervo interósseo anterior se desprendia do nervo mediano proximalmente à arcada do músculo flexor superficial dos dedos. Em 24 antebraços a ramificação do nervo interósseo anterior ocorreu proximalmente à arcada do músculo flexor superficial dos dedos em 26, distalmente. Conclusão: As bandas fibrosas formadas pelas cabeças umeral e ulnar do músculo pronador redondo, a arcada fibrosa do músculo flexor superficial dos dedos e o músculo de Gantzer, quando hipertrofiado e posicionado anteriormente ao nervo interósseo anterior, podem comprimir o nervo contra estruturas profundas, alterar seu curso normal, por estreitar o espaço de sua passagem, causar alterações no músculo flexor longo do polegar e no flexor profundo dos dedos da mão.

Anterior interosseous nerve: anatomical study and clinical implications.

OBJECTIVE: The goal of this study was to describe anatomical variations and clinical implications of anterior interosseous nerve. In complete anterior interosseous nerve palsy, the patient is unable to flex the distal phalanx of the thumb and index finger; in incomplete anterior interosseous nerve palsy, there is less axonal damage, and either the thumb or the index finger are affected. METHODS: This study was based on the dissection of 50 limbs of 25 cadavers, 22 were male and three, female. Age ranged from 28 to 77 years, 14 were white and 11 were non-white; 18 were prepared by intra-arterial injection of a solution of 10% glycerol and formaldehyde, and seven were freshly dissected cadavers. RESULTS: The anterior interosseous nerve arose from the median nerve, an average of 5.2 cm distal to the intercondylar line. In 29 limbs, it originated from the nerve fascicles of the posterior region of the median nerve and in 21 limbs, of the posterolateral fascicles. In 41 limbs, the anterior interosseous nerve positioned between the humeral and ulnar head of the pronator teres muscle. In two limbs, anterior interosseous nerve duplication was observed. In all members, it was observed that the anterior interosseous nerve arose from the median nerve proximal to the arch of the flexor digitorum superficialis muscle. In 24 limbs, the branches of the anterior interosseous nerve occurred proximal to the arch and in 26, distal to it. CONCLUSION: The fibrous arches formed by the humeral and ulnar heads of the pronator teres muscle, the fibrous arch of the flexor digitorum superficialis muscle, and the Gantzer muscle (when hypertrophied and positioned anterior to the anterior interosseous nerve), can compress the nerve against deep structures, altering its normal course, by narrowing its space, causing alterations longus and flexor digitorum profundus muscles.

OBJETIVO: Analisar as relações anatômicas e as variações do nervo interósseo anterior e suas implicações clínicas. A paralisia completa do nervo interósseo anterior resulta na incapacidade de fletir as falanges distal do polegar e indicador; na incompleta, ocorre menor dano axonal e apenas o polegar ou o indicador são afetados. MÉTODO: Este estudo baseou-se na dissecção de 50 membros de 25 cadáveres, 22 eram do sexo masculino e três do feminino. A idade variou entre 28 e 77 anos, 14 da etnia branca e 11 não branca; 18 foram preparados por injeção intra-arterial de uma solução de glicerina e formol a 10% e sete foram dissecados a fresco. RESULTADOS: O nervo interósseo anterior originou-se do nervo mediano em média de 5,2 cm distal à linha intercondilar. Em 29 membros, originou-se dos fascículos nervosos da região posterior do nervo mediano e em 21 membros, dos fascículos posterolaterais. Em 41 membros, o nervo interósseo anterior posicionava-se entre as cabeças umeral e ulnar do músculo pronador redondo. Em dois membros, observou-se a duplicação do nervo interósseo anterior. Em todos os membros, registramos que o nervo interósseo anterior se desprendia do nervo mediano proximalmente à arcada do músculo flexor superficial dos dedos. Em 24 antebraços a ramificação do nervo interósseo anterior ocorreu proximalmente à arcada do músculo flexor superficial dos dedos em 26, distalmente. CONCLUSÃO: As bandas fibrosas formadas pelas cabeças umeral e ulnar do músculo pronador redondo, a arcada fibrosa do músculo flexor superficial dos dedos e o músculo de Gantzer, quando hipertrofiado e posicionado anteriormente ao nervo interósseo anterior, podem comprimir o nervo contra estruturas profundas, alterar seu curso normal, por estreitar o espaço de sua passagem, causar alterações no músculo flexor longo do polegar e no flexor profundo dos dedos da mão.