CHAPTER 33 SURAL , BIOPSY

Annette Filiatrault, DPM

A sural nerve biopsy involves the harvesting of a 3-5 cm PREO PERAITVE PREPARAII ON section of the sural nerve, often at the level of the ankle, for microscopic evaluation. It is most often performed A significant amount of preoperative preparation is on select patients with severe, progressive idiopathic required to ensure the nerve biopsy will be appropriately in which clinical and non-invasive transferred for histologic and histochemical preparation test results have remained inconclusive. The nerve biopsy and interpretation. The surgeon must first locate and may help confirm a diagnosis, distinguish between notify the nerve histopathology laboratory of the date and different types of nerve damage, and identify specific time of the anticipated surgery. This lab will have paper- inflammatory or disease conditions of peripheral . work that will be completed by the surgeon, give The abiliq. to properly perform a sural nerve biopsy instructions on preparation of the specimen for the is a service that the podiatric surgeon can offer to neurolo- surgeont hospital laboratory, and arrange transportation gists. It involves preoperative planning in conjunction with of the biopsy to their facility.' The surgeon's hospital the pathology laboratories at both the hospital at which the laboratory may need to purchase glutaraldehyde solution surgery is to take place, and the specialized neurological and dry ice as part of the nerve preparation and should histopathology laboratory where the specimen is to be sent. Iikewise be notified prior to the biopsy date. Therefore, it The actual surgical procedure is not demanding, but is best to negotiate these details at least a week prior to the requires anatomic soft tissue dissection and minimal nerve anticipated surgical date. handling for best results. Procedure INDICAIIONS The most important criteria for nerve biopsy is that the nerve be purely sensory. Resecting a nerve with any degree Several studies have demonstrated that the underlying of motor function could lead to loss of muscle strength etiology of patients presenting with peripheral neuro- and function. Tiaditionally, the sural nerve has been the pathy can be elicited by non-invasive measures in nerve of choice for histologic examination, although approximately 8Ao/o of the cases.' However, this leaves other nerves such as the superficial peroneal and super- abonr 20o/o of those patients with idiopathic peripheral ficial radial nerves are options. The sural nerve is most neuropathy. Other invasive studies besides nerve biopsy accessible just posterior to the lateral at the level include muscle biopsy (which is often performed in com- of the ankle joint. Alternatively, the sural nerve may be bination with the sural nerve biopsy) and lumbar harvested at the level of the gastrocnemius muscle belly puncture/cerebral spinal fluid analysis. A nerve biopsy inferior to the knee, particularly when a muscle biopsy is may help confirm a diagnosis, distinguish between qypes also desired, because this allows both muscle and nerve to of nerve damage, or establish a condition evident on be harvested from the same incision.'\7e have experience histologic or histochemical examination. The strategy of primarily with biopsy of the sural nerve posterior to the the interpretation is to seek out specific diagnoses with lateral malleolus. known appearances on histopathologic exam. The biopsy A firm understanding of the anatomic location of is most useful in confirming a diagnosis of peripheral the sural nerve at the level of the ankle joint is helpful for neuropathy due to , chronic inflammatory the incision placement and soft tissue dissection. demyelinating polyneuropathy (CIDP), amyloidosis, Easrwood et al detailed the distal course of the sural nerve sarcoidosis, Ieprosy, and tumor infilration.' It may also be in their dissection of 20 cadaveric lower limbs. They useful in distinguishing certain inherited myelinopathies found the sural nerve to have a relatively constant course and some axonopathies. LJnfortunately, the biopsy may and is on average 7.4 x 0.1 cm posterior to the distal tip show nonspecific results in many cases such as when the of the fibula.a Additionally, the nerve can often be peripherai neuropathy is secondary to a metabolic or palpated at this level. nutritional disorder.' T80 CHAPTER33

The procedure can be performed under intravenous will prepare the specimen for transfer to the nerve sedation and local . A bump under the histopathology laboratory. If the delivery of the specimen ro ipsilateral hip will assist access to the laterai aspect of the the neuropathology 1ab is completed in less than 6 hours ankle. An incision is placed overlying the sural nerve then it may be refrigerated and delivered on wet ice. If trans- posterior to the fibular ma.lleolus (Figure 1). The nerve is port is anticipated to be longer then 6 hours than the identified (Figure 2) and isolated with a vessel loop to specimen must be fresh frozen in dry ice. A portion of the minimize direct nerve handling. The nerve is than freed nerve specimen may be placed in a glutaraldehyde solution from its soft tissue attachments proximally and distally for semi-thin slices and evaluation under an electron micro- within the wound (Figure 3). A 3 cm secrion of nerve is scope. Results are usually available within 2 weeks typically requested by the neuropathology laboratory. depending on the nerve histopathology laboratory used. Therefore, a 5 cm biopsy is usually taken to ensure Postoperatively, the patient should expecr ro have adequate length. A sterile ruler can be used to confirm the permanent numbness on rhe lateral aspect of the foot proper length of your specimen. The nerve is transected along the course of the sural nerve. Occasionally the distally and proximally then gently wrapped in a moist patient may experience shock-like or "phantom" pains as saline sponge thar is then placed in a sterile container the healing of the remaining nerve begins; hower.er, (Figures 4, 5). The wound is irrigated and closed in layers. this is rarely permanent and can be rreared with such The sterile specimen container will immediately be medications as Neurontin or Elavil.5 taken to the hospital pathology laboratory where they

Figure 1. Skin incision lbr sural nene biops1., posterior to the lateral malleolus Figure 2. Identi$, the sural nerue within the subcutaneous tissue laver. (- 1.4 cm) overlying the sural nerve.

Figure 3. Use a vessel loop for minimal handling ofrhe nerve and carefully free Figure 4. Gently transler the nerue ro a moist sponge. the nen e from its soft tissue attachments proxiraalll. and distallr-. Ensure a length of specimen > 3 cm. CHAPTER 33 l8r

Figure 5. Place specimen (within sponge) into sterile container and transfer immediately to hospital's pathology lab for preparation.

Pathology Results

The nerve histopathology lab will primarily search for Figure 6. Axonal degeneration, such as seen here, nonspecific be consistent with certain specific diagnoses utilizing microscopic analysis of routine is but can diagnoses. In this case, the patient has a history of and specially stained sections of nerve as well as semi-thin alcholism, with \flernicke syndrome and this uonal sections under an eiectron microscope. It is important degeneration would be consistent with peripheral neuropathy secondary to alcoholism.o that the patient understand that the nerve biopsy may not yield any further information as to the cause of their peripheral neuropathy. For example, we have seen that in some cases the peripheral neuropathy had progressed to a CONCLUSION point of complete nerve fibrosis such that the underlying disease process could not be delineated. Although a sural nerve biopsy is infrequently required to Depending on the etiology, the results of any determine the underlying etiology of a patient presenting specimen may be specific or nonspecific. The nerve biopsy with peripheral neuropathy, it is a procedure that the may only serve to distinguish between types of nerve experienced podiatric surgeon is well-equipped to damage, such as demyelination versus axon degeneration perform and may be a service that the podiatrist can offer (Figure 6). \XAile it would be impossible to cover the to neurology or pathology when a nerve biopsy is deemed histopathologic findings of all peripheral neuropathies in an appropriate measure. Keys to the success of the this articie, certain neuropathies have diagnostic features procedure include preoperative coordination between evident on microscopic examination worth brief detailing. all involved hospitals for proper specimen protocol, These include amyloidosis, vasculitis, leprosy, metachro- harvesting an adequate length of specimen, utilizing the matic leukodystrophy, and various hypertrophic (onion surgical techniques of anatomic dissection and minimal bulb) neuropathies whose characteristics are enumerated in tissue handling, and the appropriate preparation and Figures 7-11.6 Additionally, Fabryt disease is marked by transfer of the nerve biopsy for microscopic evaluation. perineural and vascular infiltration of lipid and Krabbe's disease is associated with "globoid cells" (large macrophages in close association).6 182 CHAPTER33

Figure 7. Arnyloidosis: Amorphous, eosinophilic Figure 8. Leprosl': characterized by acid-f:rst organisms amyloid accumulation in nen e er.ide nt on H&E stain.. (seen here rvithin large mononuclear cells) and inflam- matoru tissue reacrion-6

Figure 9. Metachromatic leukodvsirophv: diagnostic Figure 10. Hvpertrophic (onion bulb) neuropathies: metachromatic material wirhin nene on staining with "onion bulb" is a nonspecific finding that refers to cresyl violet, toluidine blue, or pseudoisoqranine." concentricallv-aligned aggregated Schn'ann cells about Iarge axons that often result in hypertrophl' of the ne rve. Charcot-Marie-Tooth and Deie rine-Sotras disease exemplify, tvpes of hvpertrophic neuropathics characterizccl by, among other things, exuberant onion-bulb lormation.n clr{PTER 33 183

REFERENCES

1. Lubec D, M,llbacher \7, Finsterer J, Mamoli B. Diagnostic work- up in peripheral neuropathy: an analysis of 171 cases. Postrad MedJ 1999;75:723-27. 2. Requisition lorms from the University of Alabama at Birmingham, Department of Neurology, Muscle/Nerve histopathology laboratory. 3. Hurley ME, Davids -fR, Mubarak S.f. Single-incision combination biopsy (muscle and nerve) in the diagnosis of neuromuscular disease in children. J Pediat Orthop 1994;14:740-4. 4. Eastwood DM, Irgau I, Atkins RlvI. The distal course of the sural nerwe and its significance for incisions around the lateral hindfoot.

Fo ot Ank le 1992;1 3 :1 99 -202. 5. Medlineplus Medical Encyclopedia: Nene biopsy. URL http://www.nlm.r-rkh.gov/medlineplus/enry. Accessed October, 2003 6. Burger PC, Vogel FS. Surgical pathology olthe and its coverings, 2nd Ed. New York: John \7iley & Sons,1982:700-12.

Figure 11. Hypertrophic (onion bulb) neuropathy. Onion bulb under electron microscopy shows a myelinized central uon and alternating coilagen and schrvann cell la1,ers.6