Vasa Nervorum Research Articles

Vasa Nervorum in Rat Major Pelvic Ganglion are Innervated by Nitrergic Nerve Fibers

The vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. To characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation. Characterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels. MPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope. The neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31-positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra-capsular arterioles and venules, but not the capillaries were innervated by nNOS-positive nerve fibers. This study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels.

Neuropathy, neuropathic pain, and sickle cell disease

Neuropathy, neuropathic pain, and sickle cell disease

The usefulness of ICG video angiography in the surgical treatment of superior cluneal nerve entrapment neuropathy

Superior cluneal nerve (SCN) entrapment neuropathy is a known cause of low back pain. Although surgical release at the entrapment point of the osteofibrous orifice is effective, intraoperative identification of the thin SCN in thick fat tissue and confirmation of sufficient decompression are difficult. Intraoperative indocyanine green video angiography (ICG-VA) is simple, clearly demonstrates the vascular flow dynamics, and provides real-time information on vascular patency and flow. The peripheral nerve is supplied from epineurial vessels around the nerve (vasa nervorum), and the authors now present the first ICG-VA documentation of the technique and usefulness of peripheral nerve neurolysis surgery to treat SCN entrapment neuropathy in 16 locally anesthetized patients. Clinical outcomes were assessed with the Roland-Morris Disability Questionnaire before surgery and at the latest follow-up after surgery. Indocyanine green video angiography was useful for identifying the SCN in fat tissue. It showed that the SCN penetrated and was entrapped by the thoracolumbar fascia through the orifice just before crossing over the iliac crest in all patients. The SCN was decompressed by dissection of the fascia from the orifice. Indocyanine green video angiography visualized the SCN and its termination at the entrapment point. After sufficient decompression, the SCN was clearly visualized on ICG-VA images. Low back pain improved significantly, from a preoperative Roland-Morris Questionnaire score of 13.8 to a postoperative score of 1.3 at the last follow-up visit (p < 0.05). The authors suggest that ICG-VA is useful for the inspection of peripheral nerves such as the SCN and helps to identify the SCN and to confirm sufficient decompression at surgery for SCN entrapment.

Synergistic vasculogenic effects of AMD3100 and stromal-cell-derived factor-1α in vasa nervorum of the sciatic nerve of mice with diabetic peripheral neuropathy

Autologous endothelial progenitor cell (EPC) transplantation has been suggested as a potential therapeutic approach in diabetic neuropathy (DN). However, such treatment might be limited by safety concerns regarding possible unwanted proliferation or differentiation of the transplanted stem cells. An alternative approach is the stimulation of endogenous bone-marrow-derived EPC (BM-EPC) recruitment into ischemic lesions by the administration of stem cell mobilization agents or chemokines. We first tested the EPC mobilization effect of vascular endothelial growth factor (VEGF) and AMD3100 in a mouse model of diabetes and found that AMD3100 was effective as an EPC mobilization agent, whereas VEGF did not increase circulating EPCs in these animals. Because recent studies have suggested that deceased local expression of stromal-cell-derived factor (SDF)-1α in diabetes is the main cause of defective EPC migration, AMD3100 was administrated systemically to stimulate EPC mobilization and SDF-1α was injected locally to enhance its migration into the streptozotocin-induced DN mice model. This combined therapy increased local expression levels of vasculogenesis-associated factors and newly formed endothelial cells in the sciatic nerve, resulting in the restoration of the sciatic vasa nervorum. The treatment also improved the impaired conduction velocity of the sciatic nerve in DN mice. Thus, AMD3100 might be an effective EPC mobilization agent in diabetes, with local SDF-1α injection synergistically increasing vascularity in diabetic nerves. This represents a novel potential therapeutic option for DN patients.

Thunderclap headache as the main symptom of an acute aortic dissection type A

A 67-year-old Caucasian woman presented to our emergency department after the sudden onset of thunderclap headache. The pain was localized ubiquitously in the whole head with a maximum in the visceral cranium and described by the patient as of a knife-stabbing character. A loss of consciousness did not occur. The patient reported on a short-lasting episode of mainly motor aphasia immediately after the onset of the headache. The patient had no history of migraine or other forms of headache and was not taking any medication. The neurological and physical examination was unremarkable. A computer tomography (CT) of the brain showed no signs of intracerebral haemorrhage. A lumbar puncture was declined by the patient. We decided to conduct a CTangiography to detect a possible aneurysm of the intracranial vessels. The CT-examination even included a part of the ascending aorta and the aortic arch to detect a possible dissection of the proximal vertebral arteries. The CT showed a Stanford type A acute aortic dissection (Fig. 1). Furthermore the CT also showed an affection of the proximal part of the supra-aortic vessels (Fig. 2). Confronted with the radiological diagnosis, the patient reported on an aortic aneurysm which had been diagnosed approximately 6 months before. The patient did not show any of the typical symptoms or complications of an acute aortic dissection type A such as pain between the scapulae, the chest, the throat, the abdomen, dyspnoea, heart rate deficits, hypotension and shock, seizures or paresis in the clinical course at all. Subsequent cardiac surgery was conducted successfully. The patient survived without any impairment. Stanford type A acute aortic dissection presenting with headache has been reported before [1–3]. In contrast to the cases published before, headache was, apart from a doubtful short episode of motor aphasia, the only symptom of a Stanford type A acute aortic dissection in the present case. Differential diagnostic causes for the occurrence of thunderclap headache include subarachnoidal haemorrhage, intracerebral haemorrhage, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, and dissections of the extracranial vessels [4–6]. Though lacking the examination of cerebrospinal fluid, a subarachnoidal haemorrhage as the underlying cause of the thunderclap headache is not likely regarding the clinical course. Cerebral angiography as well as a doppler and duplex sonographical examination showed no signs of reversible cerebral vasoconstriction syndrome or cerebral venous sinus thrombosis. The clinical course with no other occurrence of thunderclap headache during almost a year after the present incident argues that a reversible cerebral vasoconstriction is also unlikely. A dissection of the proximal extracranial arteries accompanying the aortic dissection could be shown via CT-angiography. A possible explanation of the pain sensation might be the mechanical irritation or vasa nervorum occlusion of the cardiac plexus and the internal carotid plexus with its sympathetic nerve tract projection to the ciliary ganglion and pterygopalatine ganglion. The absence of any cardiovascular reflexes or cardiac pain during clinical observation might be due to the fact H. Rust (&) H. Kimmig Clinic of Neurology, Schwarzwald Baar Klinikum, Rontgenstr. 20, 78054 Villingen-Schwenningen, Germany e-mail: heiko.rust@googlemail.com

Pathophysiology of diabetic erectile dysfunction: potential contribution of vasa nervorum and advanced glycation endproducts

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat medically despite advances in pharmacotherapeutic approaches in the field. This unmet need has resulted in a recent re-focus on the pathophysiology, in order to understand the cellular and molecular mechanisms leading to ED in diabetes. Diabetes-induced ED is often resistant to PDE5 inhibitor treatment, thus there is a need to discover targets that may lead to novel approaches for a successful treatment. The aim of this brief review is to update the reader in some of the latest development on that front, with a particular focus on the role of impaired neuronal blood flow and the formation of advanced glycation endproducts.

Anatomical study and clinical relevance of the flexor superficialis synovial flap: an assessment of 31 hand dissections

The authors present an anatomical study of the flexor digitorum superficialis synovial flap and its clinical application for palmar soft tissue defects in hand trauma. Green latex was injected into the brachial artery of thirty-one human upper limbs from corpses donated to science. Anatomical features of this pedicled flap were assessed: arterial vascularization, dimensions and covering surface. The anatomical support of this flap is the synovial tissue of the flexor tendons, and particularly the superficial layer of the synovial system, covering the flexor digitorum superficialis (FDS) tendons in the forearm. It is vascularized by four different arteries: a constant collateral branch of the ulnar artery, and three inconstant arterial supports: from collateral branches of the superficial palmar arch, from the radial artery, and from the vasa nervorum of the median nerve. The flap is harvested from proximal to distal on the ulnar pedicle to cover the palmar soft tissue defects of the hand. A clinical application of this synovial flap is presented via a case report for covering a palmar skin defect secondary to a hand injury. The synovial flap contains a constant ulnar pedicle and could be considered a useful alternative to cover palmar soft tissue defects.

The effectiveness of methods of off-loading to prevent diabetic foot ulcers in adults with diabetes: A Systematic Review

The effectiveness of methods of off-loading to prevent diabetic foot ulcers in adults with diabetes: A Systematic Review

Role of Nitric Oxide Synthase Family in Diabetic Neuropathy

Diabetes mellitus is one of the most common chronic diseases and a major health problem in nearly all countries. Its prevalence has risen sharply worldwide during the past few decades. The increase in its prevalence is largely due to an epidemic of type 2 diabetes (T2DM) but also the type 1 diabetes (T1DM) incidence is rising all over the world. The “classical” microvascular complications of both types of diabetes are represented by diabetic retinopathy, diabetic renal disease, and diabetic polyneuropathy (DPN). The latter has known to be heterogeneous regarding symptoms, pattern of neurologic involvement, and progression in time, pathologic alterations, and underlying mechanisms. DPN results from the direct damage of peripheral nerve components and of the associated vasa nervorum. The main contributor to the DPN development is the cumulative effect of chronic hyperglycemia - duration of diabetes and level of metabolic control. Apart the major role of hyperglycemia one of the most important factor is nitric oxide (NO) system. The NO production and local release are dramatically changed and contribute to the DPN development. The process takes place by the modulation of the nitric oxide synthase (NOS) enzymes responsible for NO synthesis by the diabetic milieu. While the decline in NO bioavailability is due to the decrease in neuronal (NOS1) and endothelial (NOS3) expression, the increase of local NO levels with the formation of peroxynitrites arises from the upregulation of inducible (NOS2) protein. Thus, NOS genes became natural candidates for the study of DPN genetics. In comparison with the other diabetes microvascular complications, data regarding the genetic background of DPN are rather scarce, particularly for NOS genes. The aim of this review is to present the pathogenesis of DPN in both type 1 and type 2 diabetes and the effect of the NOS genes-NOS enzymes-NO system.

Bone marrow expression of poly(ADP‐ribose) polymerase underlies diabetic neuropathy via hematopoietic‐neuronal cell fusion

Diabetic neuropathy is the most common diabetic complication. The pathogenetic pathways include oxidative stress, advanced glycation end product (AGE) formation, protein kinase C, and NF-κB activation, as well as increased polyol flux. These metabolic perturbations affect neurons, Schwann cells, and vasa nervorum, which are held to be the primary cell types involved. We hypothesize that diabetes induces the appearance of abnormal bone marrow-derived cells (BMDCs) that fuse with neurons in the dorsal root ganglia (DRG) of mice, leading to diabetic neuropathy. Neuronal poly(ADP-ribose) polymerase-1 (PARP-1) activation in diabetes is known to generate free radical and oxidant-induced injury and poly(ADP-ribose) polymer formation, resulting in neuronal death and dysfunction, culminating in neuropathy. We further hypothesize that BM-specific PARP expression plays a determining role in disease pathogenesis. Here we show that bone marrow transplantation (BMT) of PARP-knockout (PARPKO) cells to wild-type mice protects against, whereas BMT of wild-type cells to PARPKO mice, which are normally "neuropathy-resistant," confers susceptibility to, diabetic neuropathy. The pathogenetic process involving hyperglycemia, BMDCs, and BMDC-neuron fusion can be recapitulated in vitro. Incubation in high, but not low, glucose confers fusogenicity to BMDCs, which are characterized by proinsulin (PI) and TNF-α coexpression; coincubation of isolated DRG neurons with PI-BMDCs in high glucose leads to spontaneous fusion between the 2 cell types, while the presence of a PARP inhibitor or use of PARPKO BMDCs in the incubation protects against BMDC-neuron fusion. These complementary in vivo and in vitro experiments indicate that BMDC-PARP expression promotes diabetic neuropathy via BMDC-neuron fusion.

Acute Hepatitis B Associated Polyarteritis Nodosa Presenting as Mononeuritis Multiplex

Purpose: A 39 year old male presented with a two month history of progressive weakness and neuropathic pain resulting in difficulty walking or griping objects. Physical exam was unremarkable except for bilateral weakness, decreased vibratory sense, and hypoactive but symmetric reflexes. Laboratory studies revealed elevated inflammatory markers. CT of his abdomen showed multiorgan wedge-shaped hypodensities likely representing infarction. EMG demonstrated a severe asymmetric sensory, motor polyneuropathy characterized as a mononeuritis multiplex consistent with a neurovasculitic process. Nerve biopsy revealed a massive mononuclear cell infiltration of surrounding epineural connective tissue with a marked perivascular distribution. Further studies were positive for an acute hepatitis B infection. Given the high likelihood of an acute hepatitis B associated polyarteritis nodosa (PAN), treatment with prednisone and entecavir was initiated with rapid improvement in his strength and ability to ambulate. Extrahepatic manifestations of acute HBV infection occur in approximately 20% of patients. They can involve any body system and are important to recognize as they may occur without clinically apparent liver disease and can be mistaken for an independent disease process. One of the most severe extrahepatic manifestations is PAN, which occurs in less than 1% of patients with HBV infection. However, as many as 30% of patients with PAN are infected with HBV. Pathogenesis of the peripheral neuropathy is likely from direct cytotoxicity of the virus itself on the nerve fibers, or via deposits of immune complexes on the vasa nervorum of the nerves leading to a vasculitis and subsequent ischemia of the nerve fibers. There is no apparent relationship between severity of the vasculitis and severity of the hepatic disease. Interestingly, our patient did not have an obvious hepatic response to his acute infection given his normal liver function tests despite relatively severe vasculitis. In fact, the hepatic disease is often relatively mild despite high levels of viral replication. The prognosis for PAN is usually favorable if appropriate treatment is started early. The treatment of HBV-associated PAN includes plasma exchange to clear immune complexes, antiviral treatment, and a short course of corticosteroids. Cytoxan®, used in primary PAN, promotes persistence and replication of the virus leaving the antigen-triggering factor of the disease intact. This case illustrates the importance of recognizing the extrahepatic manifestations of acute HBV infection as it significantly impacts management with a goal of halting viral replication and achieving HBe seroconversion to accomplish complete remission without relapse.

Unilateral Macroglossia as Sole Presenting Manifestation of Internal Carotid Artery Dissection

A patient presented with acute-onset, painless, unilateral enlargement of the tongue. Steroid treatment for angioedema was ineffective, and a biopsy of an apparent mass of the tongue base showed normal tissue. Subsequent magnetic resonance imaging showed enlargement, enhancement, asymmetric T2 hyperintensity of the left half of the tongue, and dissection of the left cervical internal carotid artery (ICA) at the skull base. Unilateral enlargement of the tongue due to acute neurogenic denervation may be the sole clinical presentation of a spontaneous arterial dissection at the skull base. The hypoglossal neuropathy resulted from compression by the pseudoaneurysmal ICA dilatation or ischemia from interruption of the vasa nervorum.

Periphere Fazialisparese nach Onyx®-Embolisation einer duralen arteriovenösen Fistel

Dural arteriovenous fistulas (DAVF) are intracranial vascular malformations which can cause severe complications, such as intracranial bleeding and neurological deficits. We report the case of a patient presenting with pulsatile tinnitus caused by a DAVF. The DAVF was endovascularly treated including transarterial embolization with the liquid embolic agent Onyx®. The fistula and tinnitus were cured successfully, however, the rare complication of facial nerve palsy due to reflux of Onyx® into the vasa nervorum occurred. This could be confirmed directly during surgery and by histological analysis.

Sindromi compressive dei nervi cutanei alla fascia della gamba

Entrapment syndromes are a group of peripheral nerves disorders characterized by neurological signs or vascular symptoms, due to chronic injury to the nerve as it travels from one body segment to the next. The two leading causes of this pathology are work postures and sports activities, the latter more and more common also in the elderly population. Nerve entrapment is generally caused by localized mechanical pressure from inelastic structures such as an osseoligamentous tunnel or by estrinsic compressions due to neoplasms or anatomic variations.Nerve damage is classified as neurapraxia and symptoms don’t often correlate with nerve damage or histological features. Repetitive injury to a nerve may initially result in microvascular (ischemic) changes in perineural venous system (vasa nervorum) leading to endoneurial edema formation, increase in intraneural pressures and further interference of endoneurial microcirculation with subsequent ipoxia. Injury to the outside layers of the nerve (myelin sheath) leads to perineural fibrosis and, in more advanced stages, focal segmental demyelination related to sclerosis at the area of compression. The diagnosis is made with a thorough clinical examination, allowing to identify the nerve involved in this painful condition and the area of compression and to define the severity of the disease. EMG and, rarely, MRI or echography complete the diagnostic pathway.Operative treatment is reserved for those patients in whom conservative treatment has been unsuccessful. Timing for surgery is dependent on knowing the different anatomical entrapment sites and their specific clinical presentations. Surgical treatment in the early stages of the disease is preferable, before chronic ischemic lesions lead to permanent sensory and motor impairment.

Morphological study of the vasa nervorum in the peripheral branch of human facial nerve

Given the length of axons reaching to distal regions, all peripheral nerves must derive nutrient supply not only for the nerve cell body, but also for the peripheral parts. Along the course of a peripheral nerve, in general, nutrient vessels accompany nerve fibers to peripheral regions in the form of "vasa nervorum" derived from the epineurium, reaching the endoneurium through the perineurium and forming a capillary plexus. In addition, in reconstructive procedures in plastic surgery, anastomosis of not only nerves, but also the vasa nervorum, has been reported to achieve improved outcomes. The present study therefore observed morphological features of the blood supply to the distal portion of the facial nerve in 14 sides of 14 adult cadavers (age at death, 46-86 years) under stereo microscopy after dye injection. The region of the epineurium was also observed under scanning electron microscopy (SEM). The vasa nervorum was seen to derive from a complex reticulation structure formed mainly by the superficial temporal, facial, transverse facial and zygomatico-orbital arteries with collateral supply from the supraorbital, deep temporal, buccal arteries and parotid branches. SEM showed that one capillary accompanied each perineurium in each nerve fascicle.

18. Painful Diabetic Polyneuropathy

AbstractIn the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM‐induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur.Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second‐line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.

Label-free 3D optical microangiography imaging of functional vasa nervorum and peripheral microvascular tree in the hind limb of diabetic mice.

Diabetic neuropathy (DN) is, at least in part, associated with the functional attenuation of vasa nervorum, the microvascular structure of peripheral nerves. Microvascular imaging options for vasa nervorum still remain limited. In this work, Optical micro-angiography (OMAG), a volumetric, label-free imaging technique is utilized for characterizing, with high resolution, blood perfusion of peripheral nerve in diabetic mice. We demonstrate that OMAG is able to visualize the structure of microvasculature and to quantify the changes of dynamic blood flow and vessel diameters during administration of vessel stimulator in both diabetic and normal mice. The results indicate the potential of OMAG to assess the blood supply of nerve involved in the pathology and treatment of DN.

Successful remission induction with a combination therapy of rituximab, cyclophosphamide, and steroids in a patient with refractory optic neuritis in Wegener’s granulomatosis

A 56-year old patient with a history of limited Wegener's granulomatosis presented with signs and symptoms of optic neuritis. Radiologic signs of orbital inflammation were absent. Testing of visual acuity and visual field allowed close monitoring of disease activity. Thus, rapid improvement of visual function was achieved with high-dose steroids. Despite maintenance therapy with cyclophosphamide recurrence occurred repeatedly as soon as tapering of steroids was begun. After remission induction with rituximab, the patient retained good visual function under maintenance therapy with azathioprine and low-dose corticosteroids. Optic neuritis in Wegener's granulomatosis without signs of orbital involvement is rare and most likely caused by occlusive vasculitis of the vasa nervorum. In this patient with optic neuritis refractory to conventional therapy, rituximab in combination with cyclophosphamide and corticosteroids was well tolerated and successfully used for remission induction, followed by maintenance therapy with azathioprine and low dose corticosteroids.

Effects of interleukin‐6 treatment on neurovascular function, nerve perfusion and vascular endothelium in diabetic rats

Interleukin-6 (IL-6), a member of the neuropoietic cytokine family, participates in neural development and has neurotrophic activity. Recent research has also indicated actions to improve vasa nervorum function in diabetes. Both these facets are potentially relevant for treatment of diabetic neuropathy. The aim of this study was to determine whether IL-6 treatment corrected changes in neurovascular function in streptozotocin-induced diabetic rats. After 1 month of diabetes, rats were given IL-6 for 1 month. The rats were subjected to sensory testing and measurements of nerve conduction velocities and nerve blood flow by hydrogen clearance microelectrode polarography. Further groups were used to study responses of the isolated gastric fundus and renal artery. Results were statistically analysed using ANOVA and post hoc tests. Diabetic rats showed mechanical hyperalgesia, thermal hyperalgesia, and tactile allodynia. The former was unaffected by IL-6 treatment, whereas the latter two measures were corrected. Immunohistochemical staining of dorsal root ganglia for IL-6 did not reveal any changes with diabetes or treatment. The results showed that 22 and 17.4% slowing of sciatic motor and saphenous sensory nerve conduction velocities, respectively, with diabetes were improved by IL-6. Sciatic endoneurial perfusion was halved by diabetes and corrected by IL-6. A 40.6% diabetic deficit in maximal non-adrenergic, non-cholinergic relaxation of gastric fundus to nerve stimulation was unaffected by IL-6. Renal artery endothelium-dependent relaxation was halved by diabetes, the endothelium-derived hyperpolarizing factor (EDHF) component being severely attenuated. IL-6 did not affect nitric oxide-mediated vasorelaxation, but markedly improved EDHF responses. IL-6 improved aspects of small and large nerve fibre and vascular endothelium dysfunction in diabetic rats. The functional benefits related to increased nerve blood flow via an EDHF mechanism, and IL-6 could have therapeutic potential in diabetic neuropathy and vasculopathy, which should be further evaluated.

Utilidad del tratamiento de sustitución enzimática en la enfermedad de Fabry

The lysosomal deposit of sphingolipids secondary to alpha-galactosidase-A deficiency causes Fabry disease. The deposit in the endothelial cells of the vasa nervorum and the small caliber axons, among other structures, results in the characteristic painful neuropathy. It is our objective to present the findings of the neuropathy evaluation before and after 18 months of agalsidase beta enzyme replacement therapy. A neurological exam, a neurophysiological study measuring sensory and motor conduction velocities and amplitudes and a quantitative sensory testing were performed on 5 patients with confirmed Fabry disease; quantification on pain measurement scales was also done. Prior to treatment, no anomalies were found in the conduction velocities or the compound muscular action potential amplitudes; the quantitative sensory test was abnormal in all patients. After treatment, improvement was seen in the pain scales and the quantitative sensory test. Enzyme replacement therapy with agalsidase beta demonstrated subjective and objective benefits related to the painful neuropathy of Fabry disease.