Ischemic Neuropathy Research Articles

Painless acute aortic dissection presenting as left lower extremity numbness

Acute aortic dissection may have variable presentations, making the diagnosis clinically challenging. Acute neurologic syndromes secondary to dissection of the aorta are uncommon. However, including aortic dissection in the differential diagnosis is imperative. This report describes the first reported case of an acute thoracic aortic dissection presenting with the chief complaint of unilateral lower extremity numbness. Peripheral ischemic neuropathy as the result of vascular occlusion is uncommon. The pathophysiology and clinical manifestations of ischemic neuropathies in the setting of acute aortic dissection are discussed.

Optic disc drusen and retinal ganglion cell apoptosis

A patient with optic disc drusen and life-long low systemic blood pressure suffered several successive neuro-ophthalmic manifestations over a 30-year period (probably bilateral juvenile disc and preretinal hemorrhages, unilateral probably ischemic optochiasmatic neuropathy, established progressive night blindness, and mimic open-angle glaucomatous field loss), but always had normal intra-ocular hydrodynamics and pressure. Each of these manifestations may possibly be drusen-related, but may also appear independently of drusen. Drusen-related apoptosis of retinal ganglion cells may be the reason, explaining the ascending, evenly distributed, axonal optochiasmatic atrophy. In mimic open-angle glaucomatous disease cases with a similar evolution of visual fields but without drusen, axonal atrophy and (primary) loss of retinal ganglion cells has been reported as the only striking histopathological feature.

NECROTIZING PERIPHERAL NERVE VASCULITIS

Necrotizing vasculitis of the type in polyarteritis nodosa is a treatable cause of neuropathy. The diagnosis must be confirmed histologically by demonstration of characteristic arterial lesions in nerve and muscle biopsy specimens. Ischemic neuropathy which results from occlusion of nerve arteries in polyarteritis nodosa also occurs as a consequence of inflammatory arterial lesions in other connective tissue disorders, in some infectious neuropathies and in patients with malignant lymphomas. Patients with vasculitic neuropathy may also present with isolated peripheral neuropathy.

Participation in the Ischemic Optic Neuropathy Decompression Trial: sex, race, and age

Background The Ischemic Optic Neuropathy Decompression Trial (IONDT) is a randomized, single masked, multicenter trial designed to assess the safety and efficacy of optic nerve decompression surgery compared with careful follow-up in patients 50 years or older with non-arteritic anterior ischemic neuropathy (Naion).Objectives To examine and evaluate the sex, race, and age distributions of the screened, and subsequently enrolled, IONDT population, especially the proportions of female, minority, and elderly patients, and demographic characteristics of clinical center investigators, the geographical location of IONDT Clinical Centers, and the referral patterns of local physicians.Setting Twenty-five U.S. clinical centers.Participants There were 1,681 referrals to the Clinical Centers; an Eligibility Screening Form providing demographic information was completed for 1,152.Findings Forty-three percent (495/1,152) of screened cases were women. Seven percent (85/1152) were minorities: 33 African-Americans, 34 Hispa-nics, 17 Asians, and 1 Native-American. The average age was 66 ± 10 years with a range of 22-92 years of age. Of the 1,152 referred patients, 305 were eligible for randomization; 258 (85%) of these agreed to participate in the trial. The demographic makeup of the randomized IONDT patients was similar to that of the screened population.Conclusions Women and the elderly are well represented in the IONDT. Because the number of participating minorities was low, we cannot reliably assess their level of participation. Both a low incidence of NAION in minori-

Anterior visual pathway gliomas.

The benign anterior visual pathway glioma undoubtedly is the most controversial subject in neuro-ophthalmology. Although we are persuaded by the evidence that they are true neoplasms rather than hamartomas, the controversy over their biological nature seems moot, as they have a low growth potential. That is not to say that serious visual loss is not common or that, in some cases (especially among those lesions arising in the chiasmalhypothalamic region), tumor-related death and disability cannot occur. These posteriorly located lesions may cause hydrocephalus, and shunting is required if that occurs. The need for shunting in such cases may be the only point on which experts agree. What has yet to be established is whether any of the forms of therapy now available for anterior visual pathway gliomas without hydrocephalus is better than no treatment. Surgery, radiation, and chemotherapy all carry risks. A randomized, controlled study, if feasible, would be apt to settle the issue. The low incidence of these tumors might frustrate attempts to complete such an investigation in a reasonable period. A team of physicians should manage patients with benign anterior visual pathway gliomas. Radiologists, neurologists, neurosurgeons, radiation oncologists, pediatricians, endocrinologists, and oncologists all have a role, but the neuro-ophthalmologist should be the leader. Neuro-ophthalmologists are in the unique position of being able to recognize and document changes in the patient's visual function. Furthermore, neuro-ophthalmologists, being disinterested, are free to choose without bias from among the various management options. The malignant anterior visual pathway glioma is not a subject of controversy. The clinical features at presentation are apt to be misinterpreted as evidence of an inflammatory or ischemic neuropathy rather than the announcement of a fatal brain tumor. Though these patients receive radiotherapy and chemotherapy, these measures have not improved survival significantly, and the outcome is uniformly fatal. The only positive thing that can be said about the malignant gliomas of the anterior visual pathway is that they are so rare.

Magnetic resonance imaging in a case of migraine with ophthalmoplegia

We present the case of a migrainous girl who suffered an episode of migraine-like headache associated with ophthalmoplegia. MRI showed reversible enhancement and thickening of the cisternal portion of the oculomotor nerve. This finding suggests a mechanism different from diabetic ischaemic neuropathy, as similar MRI abnormalities were rarely reported in diabetic ophthalmoplegia. The MRI findings are most in favour of an inflammatory cause.

A bcl-2 expressing viral vector protects cortical neurons from excitotoxicity even when administered several hours after the toxic insult

The product of the bcl-2 oncogene has been shown to play an important role in apoptosis and programmed cell death. In this study, a herpes simplex virus type-1 vector was constructed to carry the human bcl-2 gene. The possible role of bcl-2 in protecting neurons from excitoxicity was investigated by using the viral vector to deliver the gene into neuronal cultures before or after the cells were exposed to glutamate under conditions in which 50–80% of neurons died. Infection with the bcl-2 expressing vector 24 h prior to glutamate treatment effectively prevented the cell death that normally follows this treatment. Moreover, infection with the vector as late as 8 h after the glutamate insult still resulted in substantial neuroprotective effects. These results have potential implications for new therapies in stroke or ischemic neuropathies.

Gastric Helicobacter pylori infection as a cause of idiopathic parkinson disease and non-arteric anterior optic ischemic neuropathy

The mechanisms of pathogenesis for both idiopathic Parkinson disease and nonarteritic anterior optic ischemic neuropathy are unknown. A study has shown that, in both diseases, there is a higher prevalence of gastrointestinal ulcers than in age- and sex-matched controls or than in the reported rates for the general population. It is proposed that gastric Helicobacter pylori infection may be a cause of both these diseases.

96/05441 Repowering of the Kelenfold district heating plant

Carbon monoxide (CO) is a colorless, odorless, nonirritant gas that accounts for numerous cases of CO poisoning every year from a variety of sources of incomplete combustion of hydrocarbons. These include poorly functioning heating systems, indoor propane-powered forklifts, indoor burning of charcoal burning briquettes, riding in the back of pick-up trucks, ice skating rinks using propane-powered resurfacing machines, and gasoline-powered generators that are not in correct locations. Once CO is inhaled it binds with hemoglobin to form carboxyhemoglobin (COHb) with an affinity 200 times greater than oxygen that leads to decreased oxygen-carrying capacity and decreased release of oxygen to tissues leading to tissue hypoxia. Ischemia occurs with CO poisoning when there is loss of consciousness that is accompanied by hypotension and ischemia in the arterial border zones of the brain. Besides binding to many heme-containing proteins, CO disrupts oxidative metabolism leading to the formation of free radicals. Once hypotension and unconsciousness occur with CO poisoning, lipid peroxidation and apoptosis follow. Because COHb has a short half-life, examination of other biomarkers of CO neurotoxicity that reflect inflammation or neuronal damage has not demonstrated consistent results. The initial symptoms with CO exposure when COHb is 15–30% are nonspecific, namely, headache, dizziness, nausea, fatigue, and impaired manual dexterity. However individuals with ischemic heart disease may experience chest pain and decreased exercise duration at COHb levels between 1% and 9%. COHb levels between 30% and 70% lead to loss of consciousness and eventually death. Following resolution of acute symptoms there may be a lucid interval of 2–40 days before the development of delayed neurologic sequelae (DNS), with diffuse demyelination in the brain accompanied by lethargy, behavior changes, forgetfulness, memory loss, and parkinsonian features. Seventy-five percent of patients with DNS recover within 1 year. Neuropsychologic abnormalities with chronic CO exposure are found even when magnetic resonance imaging (MRI) and magnetic resonance spectroscopy are normal. White-matter damage in the centrum semiovale and periventricular area and abnormalities in the globus pallidus are most commonly seen on MRI following CO exposure. Though not as common, toxic or ischemic peripheral neuropathies are associated with CO exposure in humans and animals. The cornerstone for treatment for CO poisoning is 100% oxygen using a tight-fitting mask for greater than 6 hours. The indications for treatment with hyperbaric oxygen to decrease the half-life of COHb remain controversial.

Effect of Levodopa and Carbidopa on Recovery of Visual Function in Patients With Nonarteritic Anterior Ischemic Optic Neuropathy of Longer Than Six Months' Duration

We conducted a pilot clinical trial to determine the efficacy of levodopa in promoting visual recovery in eyes with nonarteritic anterior ischemic optic neuropathy of greater than six months' duration. This prospective, randomized, double-masked, placebo-controlled clinical trial involved 20 subjects with nonarteritic anterior ischemic optic neuropathy of 30 months' mean duration. Subjects were randomly assigned to receive either low-dose levodopa and carbidopa or a placebo for three weeks. At 12 weeks after the baseline visit, the levodopa group then was provided a higher, conventional dose of levodopa and carbidopa for three more weeks. Change in visual function was monitored at four, 12, 16, and 24 weeks after the baseline visit. At 12 weeks after the baseline visit, the levodopa group experienced a significant (P = .016) mean difference in improvement of visual acuity of 5.9 letters from the placebo group. At 24 weeks after the baseline visit, a significant treatment effect (P = .036) for visual acuity was still evident; the levodopa group had a mean gain in improvement of 7.5 letters difference from baseline from the placebo group. Three subjects in the levodopa group experienced a doubling of the visual angle as denoted by a gain of at least 15 letters. Significant improvement was not observed for color vision (P = .82) or mean deviation of visual field loss (P = .82). The study found significant improvement of visual acuity among subjects receiving levodopa and carbidopa despite long-standing visual loss from nonarteritic anterior ischemic neuropathy. Confirmation of our results is awaited from larger population studies and with a longer follow-up time interval regarding the efficacy of levodopa in reversing visual loss in this disease.

Pathology of acute and chronic ischaemic neuropathy in atherosclerotic peripheral vascular disease.

The peripheral nerve pathology in ischaemic limbs with atherosclerotic peripheral vascular diseases (PVD) is difficult to ascertain because of the limited number of reports. In addition, it has been debated whether chronic ischaemia per se could cause morphological abnormalities in peripheral nerves. In this prospective study, we examined pathological findings in the sural, saphenous, deep peroneal, superficial peroneal and tibial nerves, taken from seven acutely and nine chronically ischaemic amputated legs in which ischaemia was due to non-diabetic severe PVD. For morphological comparison, nerves were also taken from amputated legs without ischaemic disease and those in which PVD was associated with diabetes. In acutely ischaemic nerves, pathological changes were dependent upon the duration of ischaemia. Axonal degeneration of both myelinated and unmyelinated nerve fibres (MFs and UMFs) with occluded vessels was prominent, if acute ischaemia was present for > 24 h. Focal lesions, a hallmark of acute ischaemic neuropathy, were seen in both acute and chronic PVD nerves. Chronic PVD nerves also revealed considerable variations in the density of MFs between the fascicles of individual nerves and between the nerves of individual subjects: demyelination and remyelination, endoneurial oedema particularly at the subperineurial region, swollen endothelial cells, various but infrequent axonal changes, and relative preservation of UMFs were also seen. All pathological changes found in acute and chronic PVD nerves, except for a high rate demyelinated and remyelinated nerve fibres, have been described in experimental models of acute ischaemic/reperfusion injury. Demyelination could be induced by chronic ischaemia. Thus, pathological alterations in chronic ischaemic neuropathy may be due to the combined effects of acute ischaemia/reperfusion and chronic hypoxia.

Progressive Systemic Sclerosis Associated with Multiple Mononeuropathy

Progressive systemic sclerosis (PSS) is a chronic connective tissue inflammatory disease which commonly attacks the skin and the visceral organs, but rarely the peripheral nervous system. The aim of this study was to investigate PSS accompanied by peripheral neuropathy clinically, electrophysiologically and pathologically from a sural nerve biopsy. Two women suffering from PSS but without any other collagen disease were studied. Both patients developed peripheral neuropathy with multiple mononeuropathy of the limbs, and in one woman, in the trunk as well. A biopsy of the sural nerve revealed axonal and myelin segmental degeneration, loss of large myelinated fibers and an increase of collagen fibers, but there was no evidence of vasculitis. An electron microscopic examination revealed degenerated axons, disrupted myelin sheaths and multilayered basal lamina in the capillaries. Mononeuropathy in PSS suggests that ischemic neuropathy may be related to the immune-mediated vasculopathy.

Induction of p75 NGFR in human diabetic neuropathy

In this immunohistochemical study we investigated the expression of low-affinity NGF receptor (p75 NGFR) in peripheral nerves from 16 patients with type I or type II diabetes mellitus. Fourteen nerves from age-and sex-matched normal individuals and nine nerves from non-diabetic patients with ischemic neuropathy served as controls. All nerve samples were preliminarily examined by standard histology, fiber teasing and electron microscopy. Increased p75 NGFR immunoreactivity was detectable within the endoneurium of cross-sections from ischemic and particularly from diabetic nerves. Immuno-teasing demonstrated that p75 NGFR immunostaining was distributed along the entire length of isolated nerve fibers undergoing axonal degeneration. Quantitative assessment of p75 NGFR immunoreactivity, performed by histospectrophotometry and expressed as percentage of adsorbance, was 21.20 ±3.50 in nerves from diabetic patients, 13.35 ±3.62 in nerves from non-diabetic patients with ischemic neuropathy and 9.02 ± 2.75 in normal controls. The increased expression of p75 NGFR in diabetic nerves is consistent with an axonopathic defect and further suggests involvement of NGF and other neurotrophins in the pathogenesis of human diabetic neuropathy.

Pathogenesis and management of upper-extremity ischemia following angioaccess surgery.

Thirty-four patients with end-stage renal disease requiring hemodialysis developed over the course of 7 years (1987-1994) severe ischemia in the extremity carrying the angioaccess secondary to arterial 'steal'. Seven of these patients were treated with access ligation, 4 with banding reducing the flow through the access, and 23 with ligation of the artery distal to the inflow of the arteriovenous fistula and establishing of an arterial bypass from a point 5 cm proximal to the fistula to the distal artery. Of the 7 patients who underwent ligation, 5 had complete resolution of symptoms, 1 had persistent pain, and 1 patient had residual ischemic neuropathy. Of the 4 patients who underwent banding, 3 lost their access due to thrombosis shortly after the banding procedure, and in 1 patient partial resolution of symptoms was achieved. Of the 23 patients who underwent arterial ligation-bypass procedure, all showed immediate signs of improvement. One patient who presented with advanced gangrene eventually required amputation, and 3 patients had some residual symptoms. The cumulative patency of the access with this procedure was 73% at 1 year and 45.5% at 2 years. The patency for the bypass was 95.6% at 1 and 2 years. The arterial ligation-bypass procedure is currently the treatment of choice for patients developing severe ischemia secondary to 'steal' following construction of an arteriovenous fistula for dialysis.

Hand ischemia in patients with hemodialysis access grafts: angiographic diagnosis and treatment.

To determine the cause of symptoms and efficacy of transcatheter therapy in a series of patients with dialysis grafts and hand pain referred for arteriography. Thirteen patients with 14 hemodialysis grafts underwent arteriography for possible hand ischemia. The sites of proximal graft anastomosis were the distal radial artery (n = 6) and the mid- to distal brachial artery (n = 6). Transcatheter therapy was performed via the graft or by antegrade brachical puncture. The cause of symptoms was ischemia from obstructive arterial disease in seven cases (three with superimposed steal), graft steal alone in three, ischemic monomelic neuropathy in two, and carpal tunnel syndrome in two. Five arterial stenoses were treated with angioplasty, with improvement or resolution of symptoms in four patients. In this group, symptoms were usually the result of inflow or outflow arterial disease, alone or in combination with graft steal. Transcatheter therapy (angioplasty or embolization) is effective in selected cases.

Reduction of Gangrene and Amputations in Diabetic Renal Transplant Patients: the Role of a Special Foot Clinic

This 4-year prospective study investigated the reasons for high levels of gangrene and major amputation in diabetic renal transplant patients and whether regular multidisciplinary foot care could reduce morbidity. All foot lesions were documented and investigated in 50 diabetic patients, mean age 49.2 +/- 11.0 (SD) years, duration of diabetes 25.3 +/- 9.0 years, time since renal transplantation 60.2 +/- 35.1 months, who attended a special foot clinic monthly for education, vascular and neurological assessment, podiatry and footwear. Foot lesions included: neuropathic ulcers, ischaemic ulcers, traumatic lesions, Charcot's arthropathy, pathological fracture. Treatment included antibiotics, podiatry, footwear, and angioplasty or distal bypass where appropriate. Only 13 patients were deemed ischaemic but peripheral neuropathy was a very common finding (mean VPT 24.8 +/- 12.9 V). Gangrene and major amputations showed a decrease on previous years and healing times for lesions were similar to those previously reported in diabetic patients without renal transplants. The majority of foot lesions, both in soft tissue and bone, were related to neuropathy and trauma and responded well to optimal foot care within the renal unit. Gangrene and major amputations were usually preventable.

Postoperative Ischemic Optic Neuropathy

Postoperative Ischemic Optic Neuropathy

Liver transplant after massive spontaneous hepatic rupture in pregnancy complicated by preeclampsia

Spontaneous hepatic rupture associated with preeclampsia is a rare but life-threatening situation. Several different surgical treatments have been described, depending on the severity of the rupture. Liver transplantation has become the mainstay for patients with end-stage liver disease. Transplantation in the setting of liver trauma or massive parenchymal disruption is not well defined. To our knowledge, this treatment has not been reported for spontaneous hepatic rupture in pregnancy. Massive, spontaneous hepatic rupture occurred in a patient at 36 weeks' gestation as a result of severe preeclampsia. Conventional surgical therapies were unsuccessful in controlling the massive hemorrhage. As a life-saving measure, the patient underwent total hepatectomy with the creation of an end-to-side portcaval shunt, thereby rendering the patient anhepatic. The patient was listed as urgently needing a liver for transplantation through the United Network for Organ Sharing. A suitable donor liver was located approximately 8 hours after the emergency hepatectomy. The patient underwent orthotopic liver transplantation after being maintained in an anhepatic state for almost 13 hours. The patient was discharged on postoperative day 41, suffering only from some ischemic lower extremity neuropathy secondary to hypovolemic hypotension occurring during the hepatectomy procedure. In the reported case, spontaneous hepatic rupture resulted in a massive hemorrhage that could not be controlled by previously reported techniques and required total hepatectomy followed by liver transplantation.

Ischemic Monomelic Neuropathy: An Under-Recognized Complication of Hemodialysis Access

During the past 3 years six episodes of ischemic monomelic neuropathy (IMN) have been identified in five patients as a complication of upper extremity dialysis grafts. All patients had long-standing insulin-dependent diabetes, peripheral neuropathy, and brachial artery graft origins, whereas 60% had peripheral vascular disease. Five episodes occurred immediately after graft placement, whereas one was due to a graft-related thromboembolus. Diagnostic delay was common with initial findings attributed to anesthesia, positioning, or surgical trauma. Electrophysiologic studies showed underlying diabetic neuropathy with severe multifocal neuropathy distal to the grafts. Digital pressure indices were reduced but there was no critical ischemia. In three cases ischemia was completely corrected with improvement in one. One patient had proximal balloon angioplasty with no improvement and of the two untreated patients, one improved slightly. Ischemic monomelic neuropathy is a rare but disabling complication of dialysis access in diabetic uremic patients. Its occurrence is unpredictable and diagnostic delay is common. Correction of ischemia is indicated but usually does not improve the neuropathy. Prevention requires further research to more accurately characterize the patients at risk.

UK Prospective Diabetes Study XII: Differences Between Asian, Afro‐Caribbean and White Caucasian Type 2 Diabetic Patients at Diagnosis of Diabetes

Clinical and biochemical variables and prevalence of complications at diagnosis of diabetes were assessed in 5098 Type 2 diabetic patients in the UK Prospective Diabetes Study of whom 82% were white Caucasian, 10% Asian of Indian origin, and 8% Afro‐Caribbean. The Asian patients were (p < 0.001) younger (mean age 52.3, 47.0, 51.0 years), less obese (BMI 29.3, 26.7, 27.9 kg m−2), had a greater waist‐hip ratio, lower blood pressure (systolic 145, 139, 144, diastolic 87, 86, 89 mmHg) and prevalence of hypertension. They were more often sedentary (19, 39, 15%), more often abstained from alcohol (21, 55, 25%) and had a greater prevalence of first degree relatives with known diabetes (36, 44, 34%). The Afro‐Caribbean patients had (p < 0.001) higher fasting plasma glucose (11.9, 11.3, 12.5 mmol l−1), more severely impaired β‐cell function (45, 35, 28% normal) and less impaired insulin sensitivity (23, 19, 27% normal) by homeostasis model assessment, lower triglyceride (1.8, 1.8, 1.3 mmol l−1), and higher HDL‐cholesterol (1.05, 1.03, 1.17 mmol l−1). Prevalence of a history of myocardial infarction, stroke or intermittent claudication at diagnosis was similar. The prevalence of ischaemic ECG (Minnesota code), microalbuminuria (urine albumin >50 mg l−1), retinopathy (‘191’ grading of retinal photographs), and neuropathy (abnormal vibration perception threshold or absent leg reflexes) was also similar. At diagnosis of Type 2 diabetes there were no differences in prevalence of complications between white Caucasian, Asian, and Afro‐Caribbean patients although differences were found in other clinical and biochemical variables.