Spectrum of diabetic neuropathies.

The diabetic state results in neuropathy. The main causative mechanism is hyperglycemia, although microvascular involvement, hypertriglyceridemia, as well as genetic and immune mechanisms may be contributory. There is a growing spectrum of types of diabetic neuropathies that differ based on the type of fibers involved (e.g. myelinated, unmyelinated, autonomic, somatic), distribution of nerves involved, and mechanisms of neuropathy. The most common type is distal sensory neuropathy (DSN), which affects the distal ends of large myelinated fibers, more often sensory than motor, and is often asymptomatic. The next-most common is distal small fiber neuropathy (DSFN), which largely affects the unmyelinated fibers and carries the phenotype of burning feet syndrome. Diabetic autonomic neuropathy (DAN) occurs when widespread involvement of autonomic unmyelinated fibers occurs, and patients can be incapacitated with orthostatic hypotension as well as neurogenic bladder and bowel involvement. Radiculoplexus diabetic neuropathy causes proximal weakness and pain, usually in the lower extremity, and has a combination of immune, inflammatory, and vascular mechanisms. The nerve roots and plexus are involved. These patients present with proximal weakness of a subacute onset, often with severe pain and some autonomic failure. Finally, rapid and sustained reduction of blood glucose can result in treatment-induced diabetic neuropathy (TIND), which largely affects the sensory and autonomic fibers. This occurs if HbA1c is rapidly reduced within 3 months, and the likelihood is proportional to the original A1c and the size of the reduction.

Determination of vagal baroreflex sensitivity in normal subjects.

INTRODUCTION: The Valsalva maneuver (VM) is used widely to quantify the sensitivity of the vagal baroreflex loop (vagal baroreflex sensitivity, BRS_v), but most studies have focused on the heart rate (HR) response to blood pressure (BP) decrement (BRS_v↓), even though the subsequent response to an increment in BP after the VM (BRS_v↑) is important and different. METHODS: We evaluated recordings of HR and BP in 187 normal subjects during the VM and determined both BRS_v↑, as determined by relating HR to the BP increase after phase III and BRS_v↓. RESULTS: BRS_v↑ was related inversely to age. In addition, BRS_v↓, age, and magnitude of phase IV were independent predictors of BRS_v↑ in a multivariate model, accounting for 47% of the variance of BRS_v↑. CONCLUSIONS: The results indicate that both BRS_v↑ and BRS_v↓ become blunted with increasing age and that these indices relate to each other.

Behçet disease presenting with neurological complications immediately after conversion from conventional cyclosporin A to microemulsion formulation.

A 53-year-old man with Behçet disease was treated with conventional cyclosporin A (CyA), because of refractory bilateral uveitis. Immediately following the conversion from conventional CyA to a microemulsion formulation, he presented with neurological complications. The neurological findings, pleocytosis of the cerebrospinal fluid (CSF) and brainstem lesions revealed by brain magnetic resonance imaging (MRI) suggested neuro-Behçet disease. After discontinuing CyA and introducing oral prednisolone, the neurological symptoms, pleocytosis of CSF and brainstem lesions on MRI improved. Although the microemulsion formulation, which can maintain a stable level of blood CyA, is a useful agent for the control of ocular lesions in Behçet disease, the resulting abrupt increase in blood CyA level may have induced neuro-Behçet disease.

[Diffusion-weighted magnetic resonance imaging findings at early stage of acute Wernicke encephalopathy].

We describe a patient with acute Wernicke encephalopathy (WE) in whom diffusion-weighted magnetic resonance imaging (DWI) were helpful for early diagnosis. A 66-year-old alcoholic man was admitted to our department because of recurrent mild drowsiness. Thiamine concentrations in blood were at the lower limit of normal. DWI demonstrated an abnormal signal intensity in the dorsal part of the midbrain, and high-dose thiamine therapy was started. These lesions disappeared on DWI after one month of follow-up, in association with clinical improvement. These findings suggest that DWI is useful for detecting WE at the early stage when high-dose thiamine treatment can improve the prognosis of WE.

Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports.

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition. Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms. Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine. Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue. These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

Effect of clinical clerkship on students' attitudes toward medical learning in Japan: a case study at Kinki University School of Medicine.

A 20-item questionnaire was administered to 253 physicians and 111 medical students, who did not have previous clinical clerkship experience, upon completion of their clinical clerkship. Medical students responded that they enjoyed their clinical clerkships but felt pressured and physically tired. Ninety percent of these medical students developed expectations for their career choice during their clinical clerkship. Only 18% of physicians felt that they allowed students enough chance to participate in clinical practice. We must emphasize that the success of any clinical clerkship system depends on an effective communication system between physicians and medical students.

Ischemic neurophysiological changes of rat sciatic nerve in vitro.

PURPOSE: Patients with ischemic neuropathy always have a progressive reduction in nerve conduction resulting in a transient increase in sensation, such as pain or hyperesthesia. We examined the effect of acute complete ischemia on neurophysiological functions in rat and related electrophysiological changes in ischemic nerve with adenosine 5'-triphosphate (ATP) administration. METHODS: The sciatic nerve of rat was placed directly on 16 parallel 0.5 mm diameter platinum electrodes (5 mm interelectrode distance) in a Perspex chamber bathed in Ringer's solution. The stimulus was applied through the electrode at the rostral end of the nerve, and the action potential recorded along different recording electrodes towards the caudal end of the nerve. Measurements were recorded immediately upon initial nerve placing and then 5, 10, 15, 30, 60, 90 and 120 min after nerve placing. RESULTS: We observed two major components in the monophasic compound action potential of the sciatic nerve of rats (A and B waves). Nerve conduction and amplitude of A and B waves underwent an initial increase followed by a reduction and after ATP administration, the transient augmentation of conduction velocity and amplitude in A and B waves disappeared. The median survival time of peripheral nerve was 60 min. CONCLUSION: At the onset of ischemia, the membrane Na-K pump does not work resulting in an increase of threshold potential in nerve membrane. When ATP levels further decrease, nerve function progressively fails.

A case of chorea-acanthocytosis with dysautonomia; quantitative autonomic deficits using CASS.

The purpose of this study was to quantitatively assess cardiovagal, adrenergic and postganglionic sudomotor functions in a patient with chorea-acanthocytosis. We describe a 25-year-old woman with acanthocytosis, lip and tongue biting, chorea like movements and increased levels of serum creatine phosphokinase. The patient presented with orthostatic hypotension. The heart period response to deep breathing was moderately decreased and the quantitative sudomotor axon reflex test (QSART) was mildly abnormal in the lower extremities. The composite autonomic score (CASS) for this patient was 6 points which indicates moderate autonomic failure. Although a few previous reports have described autonomic dysfunction associated with chorea-acanthocytosis and have indicated that impairment is primarily sympathetic, our case study suggests that there is also parasympathetic dysfunction. We conclude that there is widespread autonomic involvement in choreaacanthocytosis and that autonomic studies are useful in monitoring their course.

The impact of aging on vasa nervorum, nerve blood flow and vasopressin responsiveness.

OBJECTIVE: Aging impacts microvessels in a number of tissue beds. Vasopressin acts as a vasoconstrictor in most blood vessels but may also cause vasodilation. We evaluated the role of aging and vasopressin in the regulation of nerve blood flow (NBF) in rat peripheral nerve. METHODS: We undertook a dose-response study to examine the impact of aging on resting NBF and its vasoreactivity to vasopressin. Nerve blood flow was measured using microelectrode hydrogen polarography. Arginine-vasopressin was administered both intra-arterially and topically. RESULTS: In young adult rats (two months old) topical epineurial application of arginine-vasopressin produced a concentration-dependent reduction of NBF (ED50 = 3.8 x 10(-5) mol/L). Intra-arterial arginine-vasopressin also reduced NBF. Nerve blood flow was lower in aged rats (12 months old) and less responsive to topically applied vasopressin. The aging group had significantly higher concentrations of vasopressin in plasma than did the younger group. CONCLUSIONS: The results suggest that vasopressin constricts vessels in peripheral nerve and that there is an age related decline in the vasoconstrictive response to vasopressin. There may be a reduction in receptor sensitivity in vascular smooth muscle cells in peripheral nerve with increasing age.

The potency of migraine prophylaxis with nilvadipine: eight cases reported with further consideration.

Calcium antagonists are widely used in migraine prophylaxis. Flunarizine, a calcium antagonist is the most popular drug in prophylactic treatment of migraine in Japan, however, flunarizine is no longer sold in Japan. Therefore, we evaluated the effectiveness of the nilvadipine, a calcium antagonist, which has strong vasodilatatory action on cerebral vessels and is a safe drug in prophylactic treatment of migraine patients. Eight migraineurs were retrospectively studied, all patients took 4 mg of nilvadipine P.O. Nilvadipine significantly reduced migraine frequency and severity. Our results suggest that nilvadipine varies with regard to scientific trial study for prophylactic treatment of migraine in future.