Yoshiteru Urai

Effects of daily water drinking on orthostatic and postprandial hypotension in patients with multiple system atrophy.

ObjectiveIt has been demonstrated that the increased blood pressure (BP) caused by a single dose of water alleviates orthostatic hypotension (OH) and postprandial hypotension (PPH) in patients with autonomic failure (AF). The aim of this study was to evaluate the practical effect of daily water drinking on OH and PPH in the morning when patients with AF are usually most affected.MethodsIn five patients with multiple system atrophy (MSA) characterized by intractable OH and PPH, we measured seated, standing and postprandial BP in the morning without and with ingestion of 350 ml tap water at 07.30 hours for seven successive days. The changes from the basal BP level at 07.30 hours (ΔBP) were assessed as an index of the effect of water drinking.ResultsWater drinking elicited a rapid pressor response in all patients. The ΔBP during sitting, standing and after a meal following water drinking (day 1 and day 7) was significantly higher than without water drinking (day 0). The effects of reducing OH and PPH on day 7 were equivalent to those on day 1. No adverse effects associated with daily water drinking were observed, except later diuresis, which occurred in one patient.ConclusionsDaily water drinking demonstrated constant pressor effects in the morning with no severe adverse effects in MSA patients. This finding suggests that water drinking should be tried as a practical measure to prevent or reduce OH and PPH.

Absence of orbito-ocular signs in dural carotid–cavernous sinus fistula with a prominent anterior venous drainage

A 55-year-old woman developed an intractable right orbitofrontal headache. The symptoms subsided spontaneously 2 months after onset, but diplopia due to right abducens nerve palsy had occurred, and gradually worsened. Orbito-ocular signs were never observed throughout the clinical course. Brain MRI and MR angiography demonstrated abnormal signal changes corresponding to the right cavernous sinus. Angiography confirmed a dural carotid-cavernous sinus fistula (CCF) with three directional drainage routes in the arterial phase. Although the most prominent draining vein was the superior ophthalmic vein (SOV), an outflow with a high flow rate into the angular facial vein prevented prolonged enhancement of the SOV in the venous phase. These findings suggest that the absence of orbito-ocular signs in dural CCF with an anterior venous drainage could be attributed to the relief of venous hypertension of the SOV.

Paraneoplastic necrotizing myelopathy in a patient with advanced esophageal cancer : An autopsied case report

We report the first autopsied case of paraneoplastic necrotizing myelopathy associated with esophageal cancer in the literature. The patient had acute flaccid paraplegia and urinary retention, and had a good recovery of strength of both legs in response to corticosteroids. MRI showed a characteristic lesion with post-gadolinium enhancement of the cervical to mid-thoracic spinal cord at the onset, which has never been reported. Taken together, these results suggest that there is an underlying autoimmune mechanism in paraneoplastic necrotizing myelopathy.

Improvement of cardiovascular autonomic dysfunction following anti–copper therapy in Wilson’s disease

Sirs: Detailed autonomic function tests (AFTs) have recently revealed significant abnormalities in almost one-third of patients with Wilson’s disease (WD) [1–4]. However, the time course and reversibility of the autonomic dysfunction in WD are unknown [5]. In addition, it remains unclear whether or not the autonomic dysfunction results from central nervous system lesions. We report a patient with WD who underwent AFTs before and after anti-copper therapy. A 47-year-old woman was referred to our outpatient clinic because of tremors in her right arm and leg, which developed at 43 years of age. She had had a history of transient liver damage of unknown origin at 27 years of age. She had no family members with neurological and/or hepatic problems. She was alert, oriented and cooperative. The neurological examination revealed slight dysarthria and resting, postural and intention tremor involving the head and upper and lower extremities. A full-scale IQ on the Wechsler Adult Intelligence Scale-Revised Version (WAIS-R) was 78 (verbal, 89; performance, 68). A KayserFleischer (K-F) ring was found by slit lamp examination. Laboratory investigations showed decreased serum copper (20 μg/dl) and ceruloplasmin (3.0 mg/dl), and elevated urinary copper excretion (868 μg/day). The liver enzymes were normal. A liver biopsy confirmed the diagnosis of WD. T2-weighted magnetic resonance imaging (MRI) showed an increased signal in the thalamus, hypothalamus, midbrain and pons, and a decreased signal intensity in the putamen and globus pallidum (Fig. 1). Apart from lightheadedness upon standing, no clinical features of autonomic dysfunction were observed. AFTs revealed orthostatic hypotension upon a 60° head-up tilt, decreased pressor responses to isometric exercise and mental arithmetic and decreased heart rate responses to deep breathing and the Valsalva maneuver. A pressure “overshoot” during phase IV of the Valsalva maneuver was absent (Table 1). She had no other causes of autonomic dysfunction. Since she found treatment with penicillamine was intolerable, triethylene tetramine dihydrochloride (trientine) was administered alternatively at 2000 mg/day as a maintenance dose. Consequently, her tremor nearly disappeared within 24 months. A follow-up MRI made 36 months later revealed that the increased signal intensity lesions had disappeared (Fig. 1). The WAIS-R showed marked improvement (full-scale, 100; verbal, 99; performance, 101). Reassessment of AFTs no longer revealed orthostatic hypotension, and cardiovascular responses to pressor and respiratory stimuli were normal or increased toward the normal levels. The phase IV of the Valsalva maneuver showed a slight pressure “overshoot” (Table 1). In this case, AFTs before the anti-copper therapy revealed the latent sympathetic and parasympathetic dysautonomia, similar to previous reports [1–4]. In addition, this case showed for the first time LETTER TO THE EDITORS

Low-dose tacrolimus for two cases of myasthenia gravis with invasive thymoma that relapsed shortly after thymectomy.

Two patients with myasthenia gravis (Ossermann IIb) involving invasive thymoma who underwent extensive thymectomy manifested myasthenic crisis shortly after the procedure; however, both patients were treated with intravenous immunoglobulin and recovered from myasthenic crisis that had been deteriorating for about 1 week. Subsequently, the patients were administered a low-dose of tacrolimus (3 mg/day) in addition to prednisolone. Several months later, tacrolimus continued to control fluctuations of myasthenic symptoms and maintained remission in these patients. The serum titer of anti-Ach-receptor antibodies decreased in parallel with clinical improvement due to tacrolimus, and we accordingly reduced the dosage of prednisolone. Tacrolimus is a new immunosuppressive agent acting through the selective inhibition of helper-T-cell activation that can be reduced dosage of steroids and can maintain remission of myasthenia gravis with invasive thymoma.

The close relationship between life-threatening breathing disorders and urine storage dysfunction in multiple system atrophy

Survival of multiple system atrophy (MSA) depends on whether a variety of sleep-related breathing problems as well as autonomic failure (AF) occur. Since the brainstem lesions that cause respiratory and autonomic dysfunction overlap with each other, these critical manifestations might get worse in parallel. If so, the detection of AF, which is comparatively easy, might be predictive of a latent life-threatening breathing disorder. In 15 patients with MSA, we performed autonomic function tests composed of postural challenges and administered a questionnaire on bladder condition, as well as polysomnography and laryngoscopy during wakefulness and under anesthesia. Polysomnographic variables such as the apnea-hypopnea index (AHI) and oxygen saturation (SpO2) and the findings of laryngoscopy were compared with the degree of cardiac and urinary autonomic dysfunction. AHI, mean SpO2 and the lowest SpO2 showed significant correlations with urine storage dysfunction. In addition, patients with vocal cord abductor paralysis (VCAP) or central sleep apnea (CSA) contributing to nocturnal sudden death had more severe storage disorders than those without. On the other hand, no significant relationship between polysomnographic variables and orthostatic hypotension was observed except in the case of mean SpO2. These results indicate that life-threatening breathing disorders have a close relationship with AF, and especially urine storage dysfunction. Therefore, longitudinal assessment of deterioration of the storage function might be useful for predicting the latent progress of VCAP and CSA.

Assessment of autonomic dysfunction of multiple system atrophy with laryngeal abductor paralysis as an early manifestation

Laryngeal abductor palsy (LAP) is common in the advanced stages of multiple system atrophy (MSA). However, occurrence of LAP in the early stages might make a diagnosis of MSA difficult. To search for a clue to diagnosis of MSA with LAP as an early manifestation, we assessed the clinical features of autonomic dysfunction and the central cardiovascular control circuits in two MSA patients who had LAP as a cardinal symptom in the early stages. Development of autonomic dysfunction was preceded or followed by LAP. The autonomic symptom occurring predominantly in the earliest stages was urinary disturbance rather than orthostatic hypotension. Although screening cardiovascular autonomic function tests did not conclusively indicate a diagnosis of MSA, vasopressin release in response to head-up tilt and growth hormone response to clonidine administration demonstrated inappropriate responses, suggesting that the noradrenergic neurons of the caudal ventrolateral medulla were impaired. Diagnosis of atypical MSA with LAP in the early stages might be accelerated by a detailed investigation focused on urinary symptoms and neuroendocrine approaches.

The validity of a hyperventilation test for an investigation of autonomic failure : assessment in patients with multiple system atrophy and Parkinson's disease

Although heart rate (HR) responses to hyperventilation (HV) have been used as a cardiovascular autonomic function test, autonomic involvement during HV remains uncertain. To clarify the relationship between autonomic activity and cardiovascular changes during HV, we compared cardiovascular responses during HV among subjects with different autonomic function, namely 16 patients with probable multiple system atrophy (MSA), 16 with possible MSA, 28 with Parkinsons disease (PD) and 28 healthy controls. Abnormalities of cardiovascular responses to head‐up postural change and the Valsalva maneuver were definitely present in the order of probable MSA, possible MSA and PD, and abnormal HR and blood pressure (BP) responses during HV were observed in probable MSA and possible MSA, but not in PD. Unlike the significant difference in standard cardiovascular autonomic function tests, the HR and BP responses during HV were equivalent between probable and possible MSA. These findings suggest that cardiovascular control during HV may be affected not only by autonomic activity but also by other factors.

Transcranial Magnetic Stimulation with the Maximum Voluntary Muscle Contraction Facilitates Motor Neuron Excitability and Muscle Force

Three trials of transcranial magnetic stimulation (TMS) during the maximum voluntary muscle contraction (MVC) were repeated at 15-minute intervals for 1 hour to examine the effects on motor evoked potentials (MEPs) in the digital muscles and pinching muscle force before and after 4 high-intensity TMSs (test 1 condition) or sham TMS (test 2 condition) with MVC. Under the placebo condition, real TMS with MVC was administered only before and 1 hour after the sham TMS with MVC. Magnetic stimulation at the foramen magnum level (FMS) with MVC was performed by the same protocol as that for the test 2 condition. As a result, MEP sizes in the digital muscles significantly increased after TMS with MVC under test conditions compared with the placebo conditions (P < 0.05). Pinching muscle force was significantly larger 45 minutes and 1 hour after TMS with MVC under the test conditions than under the placebo condition (P < 0.05). FMS significantly decreased MEP amplitudes 60 minutes after the sham TMS with MVC (P < 0.005). The present results suggest that intermittently repeated TMS with MVC facilitates motor neuron excitabilities and muscle force. However, further studies are needed to confirm the effects of TMS with MVC and its mechanism.

Hyperventilation in autonomic failure: Letters

Hyperventilation (HV) can induce hypotension or even syncope in patients with autonomic failure (AF) (1–3). Deguchi et al. (4) investigated the validity of a HV test in patients with multiple system atrophy (MSA) and Parkinson’s disease (PD). The authors aimed to assess whether cardiovascular changes during HV were compatible with the degree of autonomic dysfunction. Patients with probable MSA had a significantly larger fall of blood pressure (BP) upon standing compared with patients with possible MSA, but the BP fall caused by HV did not differ between the groups. The PD group showed a subtle reduction of standing systolic blood pressure compared with controls, but no significant BP changes during HV. The HV test was performed without feedback of the actual carbon dioxide (CO2) levels. This may present a problem, as even small changes of CO2 levels can affect BP in AF considerably (e.g. lowering PaCO2 by 5 mmHg may decrease mean arterial pressure by 6 mmHg) (2). It is well known that nonstandardised HV tests result in considerable variation in the degree of hypocapnia (5). Furthermore, MSA may manifest with wide range of respiratory abnormalities including periodic irregular breathing, and thus more variation of hypocapnia may be expected (6). Therefore, the conclusion that the HV test is inappropriate to detect the severity of AF should be interpreted with much caution, as the main determinant of HV-induced hypotension in AF, i.e. the CO2 level, was not recorded.