Schematic diagram of a normal nerve (Illustration by Lena Julie Freund, Aachen, Germany)
The first sensory neurons are situated in the dorsal root ganglia, which are located in the intervertebral foramina, just proximal to the fusion of the anterior and posterior roots.
The peripheral nerve is composed of motor, sensory and sympathetic nerve fibres. A nerve fibre is the conducting unit of the nerve and contains the following elements: a central core, the axon and Schwann cells. Some nerve fibres are surrounded by a myelin component (myelinated nerve fibres), and others are free of such myelin sheath (unmyelinated nerve fibres) [2, 9, 17, 20].
The axons contain organelles including mitochondria, neurofilaments, endoplasmic reticulum, microtubules and dense particles. Axons originate from their corresponding neuronal cell bodies which are located in the spinal cord, dorsal root ganglia or autonomic ganglia, respectively.
The Schwann cells are the glial cells of the peripheral nervous system and located along the longitudinal extent of the axon.
In healthy peripheral nerves, nerve fibres of different diameter exist, large and small fibres. Only large fibres (>1.5 μm in diameter) are surrounded by segmental lipoprotein coating or covering of myelin. In this case the membranes of neighbouring Schwann cells wrap concentrically around a segment of the axon. The small area between the neighbouring Schwann cells is known as the “node of Ranvier”. The node of Ranvier permits ionic exchanges between the axoplasm of a nerve fibre and the intercellular space and permits saltatory conduction of a nerve action potential impulse, which jumps from one node to the next and is the basis for fast signal conduction. There is a basal lamina around each Schwann cell and its contents (Fig. 1.1 and 1.2).
The small and less myelinated fibres (<1.5 μm in diameter) are often grouped and enveloped by the membrane of a Schwann cell, which does not wrap a lipoprotein sheath around them (Remak bundles). These fibres do not have the structural capacity for saltatory conduction, and nerve impulses transmit slowly along the axon.
A Schwann cell not only provides myelins and a basal membrane as guidance for axons but, as a source of trophic and growth factors, it supports also the maintenance of its neighbouring axon.
The connective tissue which forms the supporting framework for the nerve fibres is the interfascicular endoneurium. A thin sheath of specialized perineurial cells, called perineurium, covers a bundle of nerve fibres (fascicle).
The nerve fascicles vary in number as well as in size, depending on a given nerve as well as the level of the nerve examination.
The endoneurium is a matrix of small-diameter collagen fibrils which are predominantly longitudinally oriented. Microvessels with tight junctions are found at this structure, and the tissue adjacent to these capillaries probably serves as a blood-nerve barrier additional to the endoneurial tissue itself [2, 7].
The perineurium consists of oblique, circular and longitudinal collagen fibrils dispersed amongst perineurial cells . The outer lamellae of the perineurium have a high density of endocytotic vesicles which may play a role in molecular transport, e.g. of glucose. The inner lamellae have tight junctions between contiguous perineurial cells, which may block the intercellular transport of macromolecules and crucially contribute to a blood-nerve barrier . The interruption of the perineurium can affect the function of the axons, which it encloses. The perineurium is the major source of tensile strength for nerve and is transversed by vessels which carry a perineurial sleeve of connective tissue.
The epineurium represents the connective tissue that covers the entire nerve trunk. The epineurium can extend internally to separate the fascicles (interfascicular epineurium). The layer between the epineurium and the surrounding tissue is called paraneurium.
The axoplasm contains proteins and cytoskeletal elements including microtubules and neurofilaments. The axoplasm is continuously built and sustained by axonal transport mechanisms.
The relationship between the fascicles within the peripheral nerve is constantly changing along a longitudinal course. Sunderland noted that the maximum length of nerve with a constant pattern was 15 mm .
Three types of nerves concerning their fascicular pattern can be distinguished [12, 13]:
Nerves with a monofascicular pattern.
Nerves with an oligofascicular pattern (2–10 fascicles).
Nerves with a polyfascicular pattern. For this nerve type, there are two subtypes that can be distinguished: the polyfascicular nerve with diffuse arrangement of fascicles and the polyfascicular nerve with group arrangement of fascicles.
Peripheral nerves receive the blood supply from small vessels leading to the epineurium (intrinsic), perineurium and endoneurium. The normal nerve is critically dependent upon the intrinsic blood supply and the perineurial and endoneurial vessels. The intrinsic vessels are similar to other vessels with the exception of having endothelial cells that contain tight junctions to aid in diffusion and extrusion of compounds. The intrinsic blood supply is crucial during regeneration, as the blood-nerve barrier breaks down uniformly along the nerve within days of injury, allowing large molecules, such as growth factors and immune cells, to cross and enter the endoneurial space .
The extrinsic blood supply system is composed of segmentally arranged vessels which vary in size and generally originate from neighbouring large arteries and veins. As these nutrient vessels reach the epineurium, they ramify within the epineurium and supply the intraneural plexus through ascending and descending branches [11, 12].
1.2 Classification of the Nerve Injuries
More than 70 years ago, nerve lesions were characterized as compression, contusion, laceration or division lesions. Seddon introduced in 1943 a classification system based on nerve fibre and nerve trunk pathology in three categories: neurapraxia, axonotmesis and neurotmesis .
The new classification according to Sunderland is based on histological features of the nerve trunk in 5° [18, 22] (Figs. 1.3 and 1.4):
Correlation of classifications according to Seddon and to Sunderland
By this type of lesion, there is an interruption of conduction at the site of injury. Therefore, this lesion grade corresponds to neurapraxia of Seddon classification. It is characterized by a focal demyelination. The rearrangement of the myelin sheath takes 3–4 weeks. After this period the nerve can almost regain its normal function.
This lesion corresponds to Seddon axonotmesis. The axon is severed, but the endoneurial sheath of nerve fibre and the basal lamina are preserved. The axons undergo Wallerian degeneration. The regeneration process lasts some months, depending on the distance between lesion and target muscle. The regeneration process may result nearly in a restitutio ad integrum.
The essential features of these injuries are destructions of endoneurial structures of the nerve fibres. A disintegration of axons and Wallerian degeneration and loss of the endoneurial tube continuity occur. The perineurium is kept intact. This situation leads to a certain degree of misdirection of regenerating axons, followed by extensive unrecoverable functional deficits.