Superficial Peroneal Nerve Biopsy Research Articles

Diagnostic yield of nerve biopsy in the evaluation of peripheral neuropathies

BackgroundWith progress made in neurogenetics and neuroinflammation, the indications and value of nerve biopsies in the diagnostic evaluation of peripheral neuropathies are less clear. In this study, we aimed to evaluate the diagnostic yield of nerve biopsies in patients with peripheral neuropathies. MethodsWe performed a retrospective review of nerve biopsy reports from April 1998 to June 2021 of patients with peripheral neuropathies presenting to the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. The diagnostic value of the biopsies was determined based on the criteria by Midroni and Bilbao as follows: contributive (essential and helpful), non-contributive and inadequate. ResultsA total of 107 nerve biopsies were analysed. Sixty-four (60 %) were males and the mean age was 52 years, ranging from 13 to 86 years. Ninety-four (88 %) were sural nerve biopsies; and only one patient (1 %) each had superficial peroneal and superficial radial nerve biopsy. The indications for the procedure were vasculitis (34 %), peripheral neuropathy of unknown aetiology (34 %), amyloidosis (14 %) and chronic inflammatory demyelinating polyneuropathy (10 %). In 68 (63 %) biopsies, the diagnostic value was contributive. Of these, 28 (26 %) were essential and 40 (37 %) were helpful. In contrast, 35 (33 %) biopsies were non-contributive and 4 (4 %) were inadequate. In 66 % (71/107) of cases, the nerve biopsy did not reveal a definite pathological diagnosis. However, in the remainder, a diagnosis of vasculitis (18 %, 19/107), followed by amyloidosis (10 %, 11/107) could be determined. For 32/71 biopsies with undetermined pathological diagnosis, neuropathy remained cryptogenic in 22 % (7/32) upon follow up. ConclusionsWith the exception of vasculitis and amyloidosis, there is limited value in performing nerve biopsies in the evaluation of patients with peripheral neuropathy. However, this should be interpreted with caution as the number of patients with a clinical diagnosis of vasculitis and amyloidosis were relatively larger than patients with other diagnosis. Refinement and careful selection of cases are required to increase the diagnostic yield of nerve biopsy.

A study correlating nerve biopsy with clinical diagnosis and its impact on improving management in peripheral neuropathies

BackgroundThis study attempts to evaluate the utility of nerve biopsy in complementing or redirecting clinical diagnosis. Several factors determine the diagnostic utility of nerve biopsy, the most important being pre-biopsy diagnosis, with higher diagnostic yield reported in asymmetric and multi-focal neuropathies. MethodsThis retrospective study was conducted at a tertiary care hospital in South India, wherein, patients with a clinical and electrophysiological diagnosis of peripheral neuropathy who underwent nerve biopsy between Jan 2012- Dec 2016 were reviewed. ResultsA total of 112 nerve biopsies were performed at our Institute during the study period, of which, 84 had adequate information for review and inclusion in the study. In a majority (75) Sural nerve was biopsied, followed by combined superficial peroneal nerve and peroneus tertius muscle biopsy (5).Nerve biopsy diagnosis was concordant with and helped confirm the clinical diagnosis in 43/84 (51%) cases, which included vasculitic neuropathy (20), CIDP (16), leprous neuropathy (6). In10/84 (12%) patients, the nerve biopsy diagnosis was discordant with the clinical diagnosis and helped in redirecting management. This included vasculitic and diabetic neuropathy (2 each), Charcot Marie Tooth Disease (3), and leprous neuropathy (3). In 31/85 (37%) cases with no clinically evident etiological diagnosis, nerve biopsy proved useful in establishing diagnosis in 16/31 (51%) cases aiding patient management. This included Non-systemic vasculitic neuropathy (7), leprous neuropathy (3), diabetic neuropathy (2), and Giant axonal neuropathy (1). ConclusionNerve biopsy remains a valuable tool in complementing or redirecting the clinical diagnosis, and improving the therapeutic outcomes in peripheral neuropathies. It should be done upfront in clinically idiopathic neuropathies, and early at follow up in treatment refractory neuropathies.

Nerve and skin biopsy in neuropathies.

To give an overview of recent data on the use of nerve and skin biopsy as a diagnostic tool in neuropathies. Axonal damage in a biopsy from a patient with chronic inflammatory demyelinating polyradiculoneuropathy may point to the presence of autoantibodies to paranodal proteins. In nonsystemic vasculitis of the peripheral nervous system, nerve biopsy is still the only means to make a definite diagnosis. Increased autophagy has been found in idiopathic neuropathy and may also be a common final pathway in various types of neuropathy. Nerve biopsy has unexpectedly revealed familial amyloid neuropathy in a number of cases that were taken for idiopathic, for Charcot-Marie-Tooth disease, or for chronic inflammatory demyelinating polyradiculoneuropathy. Skin biopsy can differentiate between length-dependent and non-length-dependent small fiber neuropathy, which aids in the etiological differential diagnosis. It can also be used to identify small fiber involvement in mixed neuropathies and for follow-up studies. Nerve biopsy is still the gold standard for the diagnosis of peripheral nerve vasculitis. In other indications, sural or superficial peroneal nerve biopsies are less frequently done, because less invasive methods have become available. Modern imaging methods allow localization of nerve damage, such that targeted fascicular biopsies can be done. Immunofluorescence staining of teased nerve fibers has contributed to the understanding of the pathophysiology of inflammatory neuropathies. Skin biopsy has become a routine method to diagnose small fiber neuropathy.

Chronic Eosinophillic Leukemia presenting as Peripheral Neuropathy

Chronic Eosinophilic Leukemia (CEL) is a rare form of chronic myeloproliferative disorder of unknown etiology with no data on its true incidence. The disease has a wide variety of manifestations. Literature search has not shown peripheral neuropathy as the only presentation of CEL. Our case is probably the first such report case. Here we are reporting a 45 year old male patient who presented with progressive weakness of upper and lower limbs for 6 months and weight loss for 2 months. Neurological examination revealed findings consistent with bilateral sensorimotor polyneuropathy later confirmed by nerve conduction studies. Complete blood count revealed total wbc count – 51, 870/mm3, eosinophil – 62.1% (32,315/mm3). Peripheral Blood film revealed eosinophilic leucocytosis. Superficial peroneal nerve biopsy showed mild perivascular infiltration with inflammatory cells. No granuloma or malignancy was seen. Bone Marrow examination showed hyperactive granulopoiesis with predominance of eosinophil series with progressive maturation along with presence of myeolcytes, hypersegmented eosinophils and giant eosinophils. Blast cell was around 7%. Patient was treated with imatinib and prednisolone which showed excellent response.Bangladesh Crit Care J March 2018; 6(1): 47-49

Clinical Neuropathology practice guide 3-2014: Combined nerve and muscle biopsy in the diagnostic workup of neuropathy – the Bordeaux experience

Simultaneous combined superficial peroneal nerve and peroneous brevis muscle biopsy, via the same cutaneous incision, allows examination of several tissue specimens and significantly improves the diagnosis of systemic diseases with peripheral nerve involvement. Vasculitides are certainly the most frequently diagnosed on neuro-muscular biopsies, but this procedure is also well advised to asses a diagnosis of sarcoidosis or amyloidosis. More occasionally, combined nerve and muscle biopsy may reveal an unpredicted diagnosis of cholesterol embolism, intra-vascular lymphoma, or enables complementary diagnosis investigations on mitochondrial cytopathy or storage disease.

A Clinical and Neuropathological Study of Chinese Patients with Diabetic Peripheral Neuropathy

ObjectiveTo examine whether the neuropathological and metabolic changes of peripheral nerves are correlated to clinical features in diabetes mellitus type 2 patients with peripheral neuropathy.Methods147 type 2 diabetic patients with signs/symptoms of diabetic peripheralneuropathy (DPN) aged 53.4±12.3 years and 134 healthy volunteers aged 55.5±11.7 years were investigated for fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), and red blood cell sorbitol (RBC sorbitol) in addition to nerve conduction velocity (NCV). Among the 147 diabetic patients, 10 patients underwent superficial peroneal nerve biopsy for light and electron microscopy.ResultsIn the experimental group, the levels of HbA1c and RBC sorbitol showed significant increase compared with the controlled group, whereas motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) both showed decline and SNCV decreased at a greater extent. Morphologically, there were various degrees of nerve fiber loss, associated with axon degeneration and capillary luminal narrowing in 10 patients undergone nerve biopsy.ConclusionThe metabolic change of sorbitol, the consequently observed changes in NCV and histopathology of peripheral nerves are positively correlated with the duration of diabetes and overall level of blood glucose.

Microvasculitis in Diabetic Lumbosacral Radiculoplexus Neuropathy

We present a case of a 60-year-old man with mild type 2 diabetes mellitus and step-wise progression of bilateral lower limb weakness, numbness, and pain over a 1-year period. At the time of evaluation, he used a walker. He had elevated cerebrospinal fluid protein, abnormal cooling and heat-pain thresholds on quantitative sensory testing, and nerve conduction studies/electromyography consistent with bilateral lumbosacral radiculoplexus neuropathies. Because it was not clear whether the disease was still active, a right superficial peroneal nerve biopsy was performed and showed evidence of active axonal degeneration, ischemic injury, and microvasculitis. On the basis of these results, the patient was diagnosed with diabetic lumbosacral radiculoplexus neuropathy and was treated with weekly intravenous methylprednisolone with marked improvement of neurologic symptoms and signs. This case illustrates the typical clinical, electrophysiologic, and pathologic features of diabetic lumbosacral radiculoplexus neuropathy and the utility of nerve biopsy to judge ongoing disease activity.

The use of nerve and muscle biopsy in the diagnosis of vasculitis: a 5 year retrospective study

Introduction: Peripheral nerve vasculitis is an important condition which can be diagnostically challenging and is one of the principal current indications for nerve and muscle biopsy. Previous studies have suggested...

Presence of crystalline inclusions in the peripheral nerve of a patient with IgA lambda monoclonal gammopathy of undetermined significance

Association of a peripheral neuropathy with an IgA monoclonal gammopathy of undetermined significance (MGUS) is not commonly observed and is sometimes considered as coincidental. We present a case in which the nerve biopsy revealed the presence of crystalline inclusions in the endoneurium, a very unusual finding. A 75-year-old man complained of paresthesiae in both feet and unsteady gait for 6 months. He had no weakness, but deep tendon reflexes were absent and vibratory sensation distally diminished in both legs. An IgA lambda MGUS was evidenced in his serum at 10.2 g/L with 7% plasma cells in his bone marrow and no lytic lesion at skeletal examination. A superficial peroneal nerve biopsy was performed and showed numerous crystalline inclusions in the endoneurium. These were located in the cytoplasm of macrophagic histiocytes or free in the vicinity of nerve fibers. There was also a marked loss of myelinated nerve fibers and several "onion bulb" formations surrounding either isolated remyelinating fibers or small clusters of remyelinating fibers. Such crystalline inclusions have mainly been observed in the cytoplasm of plasma cells in cases of multiple myeloma, and correspond to non-secreted IgA or IgG immunoglobulins with a kappa or rarely lambda light chain. Such inclusions have also been reported in the cytoplasm of the epithelial cells from corneal fragments, in patients with multiple myeloma or IgG MGUS, and in the tubular cells from the kidney of patients with multiple myeloma and a nephrotic syndrome. In the literature, there is only one very briefly mentioned case of neuropathy associated with a myeloma and with crystalline inclusions present in the epineurium. Thus, in dysglobulinemic neuropathy, nerve fibers can be damaged by three kinds of interstitial deposits, easily identified by immunohistochemistry and at ultrastructural examination: the well known amyloid fibrils, granulo-fibrillar deposits and also crystalline inclusions.

慢性ＧＶＨＤ経過中に慢性炎症性脱髄性多発根ニューロパチーと低Ｎａ血症をみとめた１例

A 54-year-old woman, who was treated with chemotherapy for acute lymphoblastic leukemia, developed dysesthesia in her hands and feet at the age of 50 in 2003. The following year she underwent hematopoietic stem cell transplantation. In 2005, she was diagnosed with chronic graft versus host disease (cGVHD). In December 2006, she developed dysesthesia in her face and tongue (onset). 50 days after the onset, she had a respiratory infection. 10 days later, she was hospitalized for muscle weakness of four extremities and progression of dysesthesia. Nerve conduction studies and superficial peroneal nerve biopsy revealed demyelination. After high-dose immunoglobulin therapy, her muscle strength recovered. Hyponatremia was resolved by restriction of fluid intake and administration of NaCl. We suggest immunological mechanisms such as cGVHD may cause chronic inflammatory demyelinating polyradiculoneuropathy and hyponatremia.

Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome

We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogren's syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association.

Histopathological features of X-linked Charcot-Marie-Tooth disease in 8 patients from 6 families with different connexin32 mutations.

There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of "pseudo-onion bulb" formation. There was no "naked axon" (ie, demyelinated axon), and real "onion bulb" formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions.

Histopathological features of X‐linked Charcot‐Marie‐Tooth disease in 8 patients from 6 families with different connexin32 mutations

Abstract There is still confusion as to whether X‐linked Charcot‐Marie‐Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of “pseudo‐onion bulb” formation. There was no “naked axon” (ie, demyelinated axon), and real “onion bulb” formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g‐ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon‐Schwann cell interactions.

Inexcitability of nerves in a fulminant case of Guillain‐Barré syndrome

A 45-year-old woman presented with a recent sensorimotor deficiency in all 4 limbs, and the next day she was totally paralyzed. A slight motor improvement began on day 27. The cerebrospinal fluid had normal cellularity, but the protein varied from 90 mg/dL on the first day to 800 mg/dL on day 15, and then 290 mg/dL on day 33. Electrophysiologic studies performed on days 15 and 23 revealed a universal peripheral nerve inexcitability. A superficial peroneal nerve biopsy was performed on day 23. Nine fascicles were examined on semi-thin sections and myelinated fiber damage varied greatly from one fascicle to another. At ultrastructural examination, certain axons were severely damaged, but the others were quite well preserved and were naked or wrapped in a myelin sheath presenting a multivesicular degeneration. A few fibers had a better-preserved myelin sheath that was sometimes dissociated by elongated processes from an invading histiocyte. Six cases of fulminant Guillain-Barré syndrome with inexcitability of nerves and ultrastructural examination of nerve fragments have been reported. Electrophysiologic study is often ambiguous and cannot determine the precise origin of such an axonal degeneration. Therefore, ultrastructural analysis of a nerve biopsy is mandatory in this setting.

Perineurial abnormalities in the spontaneously diabetic dog.

Structural abnormalities of the perineurium from six spontaneously diabetic dogs (diabetes duration 4-8 years and six control animals were quantified using detailed electron microscopic morphometric methods on superficial peroneal nerve biopsy specimens. Total perineurial sheath thickness (microm) was significantly increased in diabetic (8.8+/-0.6) compared to control animals (6.2+/-0.3) (P < 0.02). This was attributed to a significant increase in the mean perineurial lamellar width in diabetic (0.49+/-0.03) compared to control (0.40+/-0.01) (P < 0.04) animals. The number of lamellae also showed a non-significant increase in diabetic animals (7.8+/-0.4) compared to controls (6.9+/-0.13) (P < 0.06). There was no change in the mean interlamellar space in diabetic (0.7+/-0.05) compared to control (0.6+/-0.06) (P = 0.15) animals. The total interlamellar space was increased in diabetic (5.7+/-0.5) compared to control (4.1+/-0.36) (P < 0.04) animals. The perineurial cell basement membrane thickness (nm) was significantly increased in diabetic (126.9+/-9.8) compared to control (62.8+/-6.1) (P < 0.005) animals. The current study has demonstrated significant abnormalities of the perineurium in the spontaneously diabetic dog, which may have relevance to the pathogenesis of diabetic neuropathy.

Severe motor-dominant neuropathy with IgM M-protein binding to the NeuAcα2-3Galβ- moiety

We report the occurrence of a relapsing, severe predominantly motor neuropathy in a 75-year-old man with an IGM-κ M-protein binding to gangliosides GM2, GM3, GM4, GD1a, GT1b and LM1. Motor nerve conduction velocities were slowed with conduction block. A superficial peroneal nerve biopsy specimen revealed segmental demyelination and remyelination. The patient improved after repeated plasma exchanges, and the antibody titer decreased in association with clinical recovery. This IgM M-protein has a unique, previously unreported binding specificity for terminal NeuAcα2-3Galβ- moiety in common to all gangliosides bound by the antibody except GM2. M-proteins with this affinity may be involved in the pathogenesis of this and other cases of motor-dominant demyelinating neuropathy.

Age-dependent axonal loss in nerve biopsy of patients with xeroderma pigmentosum

We describe the histomorphometric changes in the superficial peroneal nerve biopsy from 13 patients with xeroderma pigmentosum (XP). The mean age at time of biopsy was 15 yr (range 2.5–24 yr). The clinical examination was normal in the two youngest patients and showed absence of the deep tendon reflexes, with choreo-athetosis in ten patients. In addition, in the three oldest patients there were cerebellar signs, ataxia and Babinski signs. The nerve biopsy showed an age-dependent decrease of myelinated fibres, which was mild in the youngest and severe in the oldest patients. This was associated with rare acute axonal degeneration, sparse axonal regeneration, rare axonal atrophy and few onion bulb formations. These findings suggest a neuropathic process. This neuronal degeneration seems to be a progressive and stereotyped phenomenon in XP.

Polyneuropathy associated with IgM monoclonal gammopathy

Quantitative, immunopathological, light and electron microscopic studies of superficial peroneal nerve biopsies from 31 patients with IgM monoclonal gammopathy were carried out. Six patients had Waldenström's macroglobulinemia and 25 had IgM monoclonal gammopathy of undetermined significance. Serum samples from 28 of these patients were assayed for anti-myelin-associated glycoprotein (anti-MAG) activity. Anti-MAG activity was found in 25 of the samples. There was a relationship between the widening of some myelin lamellae observed on ultrastructural examination and the serum anti-MAG activity (23 cases). Immunopathological examination showed IgM binding to myelin sheaths in 17 cases.

Atteinte du nerf sensitif dans l'amyotrophie bulbo-spinale liee a l'X (syndrome de Kennedy). Apport des donnees electrophysiologiques et histologiques

Two new cases of X-chromosome linked bulbospinal muscular atrophy associated with gynecomastia (described by Kennedy in 1968) are reported. In one patient, an electrophysiological study and a muscle nerve biopsy were performed. Motor nerve conduction studies were normal but sensory action potentials were small or unrecordable in the absence of clinical sensory loss. Superficial peroneal nerve biopsy showed axonal lesions. These findings suggest that this disease is not purely due to degeneration of spinal motor neurons and is also associated with an axonopathy.

Sensory and motor peripheral neuropathy in olivopontocerebellar atrophy.

We report the findings of an electrophysiological study in 9 patients affected by olivopontocerebellar atrophy, 4 with a dominant form and 5 with a sporadic form. Superficial peroneal nerve biopsy was obtained from 2 patients. The electrophysiological alterations were signs of collateral reinnervation and loss of motor units, decrease in sensory potential amplitude and increase in distal motor latency. Only a slight reduction in motor and sensory conduction velocity was observed in some cases. Nerve biopsy showed slight reduction of the number of myelinated fibres. In the first case, fibre diameter distribution was unimodal, due to reduction of myelinated fibres of large diameter, in the second case there was no significant alteration of the fibre distribution. In both cases short internodes were present with no signs of segmental demyelination, remyelination or axonal degeneration. The alterations observed in the peripheral nervous system are probably secondary to a lesion of the posterior root ganglion and the anterior horn cell in the spinal cord.