Physiological and clinical correlates of cardiorespiratory reflexes in diabetes mellitus.

Cardiorespiratory reflexes (CRRs) were studied by measuring heart-rate (HR) variation during 6 breaths/min respiration (delta R6) and Valsalva maneuver (VR) in 145 healthy and 417 type I (insulin-dependent) diabetic subjects. HR variation with breathing at 12 breaths/min and ventilatory response to hypercapnia/hypoxia were measured in fewer subjects. CRR results were compared with symptoms of autonomic dysfunction, the neurological examination, nerve conduction studies, and quantitative sweat testing. The objective was to compare the sensitivity of various methods of characterizing diabetic patients and to use this information when staging patients for clinical therapeutic trials. CRR responses were age dependent in both populations. Either delta R6 or VR was abnormal in 74% of diabetic patients, delta R6 being more sensitive. CRRs correlated well with the presence of symptoms of autonomic dysfunction, abnormalities on the neurological examination, results of nerve conduction studies, and sweating activity in the feet of the same patients. However, both CRRs and sweating were abnormal in a high proportion of patients without any clinical manifestations of neuropathy. The ventilatory reflex response to moderate hypercapnia/hypoxia was also measured. It was normal in most of the diabetic patients tested, including many with severe reduction of CRRs. We conclude from the combined results of CRR, ventilatory response, and other studies that the causative factors for abnormal CRR may not be confined to the vagus nerves, and that in most instances, the depressed CRR may be due to a decrease in the efficacy of sensorimotor nerve conduction around the reflex arc.

Anal muscle electromyograms differ in amyotrophic lateral sclerosis and Shy-Drager syndrome.

Electromyography (EMG) of anal sphincter muscles was different in patients with amyotrophic lateral sclerosis (ALS) and Shy-Drager syndome. In 30 patients with ALS, EMG of the external sphincter muscle was essentially normal, with no signs of denervation. In eight cases of Shy-Drager syndrome, however, motor unit potentials of the anal sphincter had highly polyphasic forms of long duration and high amplitude. In the Shy-Drager syndrome, there seems to be specific damage of lower motor neurons that innervate the external sphincter muscle of the anus.

The sweating deficiency in diabetes mellitus: methods of quantitation and clinical correlation.

A method that measures the amount of sweat evaporating from the skin was used to quantitate the sweating deficiency that accompanies diabetic neuropathy. The decreased amount of sweat secreted after pilocarpine stimulation was proportional to the reduction in number of excitable sweat glands, and to the decrease in water measured by the summed volume of all sweat droplets secreted. The results also correlated favorably with the degree of sensory loss to painful stimuli, but not to the alpha motor nerve conduction velocity or motor axon loss evaluated by muscle action potentials evoked from foot muscles. Respiratory-cardiovascular reflexes, as measured by the Valsalva ratio, were always abnormal in patients with demonstrated sweating deficiency and often in patients with normal sweat function.

Rodent eccrine sweat glands: a case of multiple efferent innervation.

The sweat territories of peripheral nerves to the hind-paw of the mouse were defined by a silastic impression mold method that allowed identification of every secreting sweat gland. It was found that the tibial, sural, saphenous and peroneal nerves all contribute to the innervation of foot pad sweat glands, and there is extensive overlapping of the sweat territories of the different peripheral nerves. Most sweat glands could be activated by electrical stimulation of axons in two or three peripheral nerves or in separate fascicles of one nerve. This was interpreted to indicate that these sweat glands receive multiple innervation and that sweat glands in the overlap regions between autonomous zones of adjacent cutaneous nerves can receive axons from each nerve. Partial denervation of sweat glands by section of one source of innervation did not prevent the gland from sweating during stimulation of intact axons to the gland, or after pilocarpine treatment. Totally denervated glands did not exhibit denervation hypersensitivity; they became unresponsive to pilocarpine, acetylcholine and adrenaline. These characteristics allowed detection of the appearance and progression of reinnervation (and reactivation) of denervated sweat glands by collateral branching from sudomotor fibers. Not only do these results increase our basic understanding of the anatomical relations between peripheral nerves and the sweat glands they innervate, but they also demonstrate that the mouse sweat gland provides a useful model system for studying neuropathology of the sympathetic nervous system.

Dissociated nystagmus in a comatose patient. A clinicopathological study.

Electro-oculographic recordings of dissociated vertical (oblique and upbeat) nystagmus were carried out in a patient in coma due to vascular lesions. Based on the clinical and neuropathological findings, it was suggested that dissociated vertical (oblique and upbeat) nystagmus in a patient in coma can be caused by bilateral lesions in the brachium pontis.

Positron emission tomography of reversible intellectual impairment induced by long-term anticholinergic therapy.

Long-term oral anticholinergic (AC) therapy can occasionally produce intellectual impairment. We investigated a patient with Parkinson's disease accompanied by intellectual impairment induced by long-term AC therapy. The intellectual impairment of the patient disappeared after cessation of AC therapy. Positron emission tomography (PET), during and after long-term oral AC therapy, revealed that it causes bilateral diffuse decrease of glucose metabolism in the cortex, basal ganglia, thalamus, hippocampus and cerebellum. Cessation of the therapy resulted in diffuse increase of glucose metabolism in all of the above regions. Cranial CT and magnetic resonance imaging (MRI) showed no abnormalities. Our results suggest that long-term AC therapy causes reversible bilateral diffuse glucose hypometabolism.

Alexia caused by a fusiform or posterior inferior temporal lesion.

We evaluated the alexia and agraphia of three patients with different lesions using Japanese kanji (morphograms) and kana (phonograms) and made a lesion-to-symptom analysis. Patient 1 (pure alexia for both kanji and kana and minor agraphia for kanji after a fusiform lesion) made more paragraphic errors for kanji, whereas patient 2 (alexia with agraphia for kanji after a posterior inferior temporal lesion) showed severe reading and writing disturbances and more agraphic errors for kanji. Brodmann Area 37 was affected in both patients, but in patient 2 the lesion was located lateral to that in patient 1. Patient 3 showed agraphia without alexia after restricted lesion to the angular gyrus. We believe that pure alexia (patient 1) results from a disconnection between the medial fusiform gyrus and posterior inferior temporal area (the lateral fusiform and inferior temporal gyri), whereas alexia with agraphia for kanji (patient 2), corresponding to lexical agraphia in Western countries, results from damage to the posterior inferior temporal area, in which whole-word images of words are thought to be stored. Furthermore, restricted lesion in the angular gyrus (patient 3) does not produce alexia; the alexic symptom of "angular" alexia with agraphia may be the result of damage to the adjacent lateral occipital gyri.

Mechanism of short-term memory and repetition in conduction aphasia and related cognitive disorders: a neuropsychological, audiological and neuroimaging study.

To evaluate the role of the sub-cortical white matter and cortical areas of the supramarginal gyrus in short-term memory impairment (shortened digit or letter span) and repetition difficulty, four patients with conduction aphasia and impaired short-term memory and two patients with only short-term memory impairment were given digit span, letter span, speech audiometry and dichotic listening tests. The results showed that in most of the patients letter span was inferior to digit span and that bilateral ear suppression in the dichotic listening test was observed in two patients with a lesion in the inferior part of the supramarginal gyrus, suggesting that what was affected was phonological information and that the supramarginal gyrus was the storage site. The overlapped lesion of conduction aphasia patients with short-term memory impairment was the periventricular white matter at the upper to middle part of the trigone, while patients with only short-term memory impairment had a lesion in the inferior supramarginal gyrus in common. Thus, damage to the periventricular white matter at the trigone may yield the phonemic paraphasia characteristic of conduction aphasia, while damage to the inferior part of the supramarginal gyrus may result in the impairment of short-term memory. We believe that as a part of the mechanisms of short-term memory and repetition, phonological information is processed in the primary auditory cortex and goes through the periventricular white matter to the inferior part of the supramarginal gyrus and is temporarily stored there.

Chronic dementia in Parkinson's disease treated by anticholinergic agents. Neuropsychological and neuroradiological examination.

Reports about chronic-onset dementia due to ACA have been rare. Here we described five patients with chronic dementia induced by ACA. We examined their clinical aspect, neuropsychological aspect, and neuroradiological aspect in detail. Our study suggests the possibility of ACA-induced chronic-onset dementia in PD patients.

A case of adenoid cystic carcinoma (ACC) of the breast and review of the utility of preoperative imaging diagnose.

A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.

Mexiletine for painful alcoholic neuropathy.

Five patients suffering from painful alcoholic neuropathy showed severe painful sensory disturbance in their extremities. Although their pain was not ameliorated by the typical usual analgesic agents, oral mexiletine (MX) therapy was remarkably effective for the pain (especially tingling and aching sensation) without major side effects. This study indicated that the minimum effective dose was 300 mg per day and the effective concentration of MX in plasma was 0.66 +/- 0.15 micrograms/ml in these patients. Thus, oral MX therapy can be a reliable treatment for pain in alcoholic neuropathy.

Portal-systemic encephalopathy and hypothalamic hypothyroidism: effect of thyroid hormone on ammonia metabolism.

We describe a 53-year-old woman with portal-systemic encephalopathy and altered thyroid function. Endocrinological studies revealed low levels of free thyroid hormone with an inappropriately low level of thyroid-stimulating hormone that responded to bolus injection of thyrotropin-releasing hormone with a normal but somewhat delayed pattern. On the diagnosis of hypothalamic hypothyroidism, she was treated with levothyroxine sodium. Thyroid hormone replacement improved not only the symptoms of hypothyroidism but the hyperammonemia and consciousness disturbance, which suggested a hitherto undescribed possibility that hypothyroidism may be an exacerbation factor of hyperammonemia and portal-systemic encephalopathy.

Elevated serum interleukin-6 in POEMS syndrome reflects the activity of the disease.

In patients with POEMS syndrome, which often accompanies plasma cell dyscrasia, the roles of interleukin-6 (IL-6) and other acute phase cytokines are unknown. Serum IL-6, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were measured by the enzyme-linked immunosorbent assay technique in 16 patients with POEMS syndrome and in patients with other neurological diseases (OND) as control. Serum IL-6 was more frequently detected and higher in active POEMS than in stable POEMS or in OND patients. No sample was positive for IL-1 beta. TNF-alpha was positive in 3 out of 7 active POEMS patients, but its significance was not definite. Serum IL-6 levels in POEMS patients reflected the disease activity but not the severity of accompanying plasma cell dyscrasia.

Reversible memory disturbance and intelligence impairment induced by long-term anticholinergic therapy.

It is controversial whether long-term anticholinergic therapy (AC-T) can cause short-term memory disturbance, long-term memory disturbance or intelligence impairment. Ninety patients with Parkinson's disease were examined prospectively to clarify the existence of memory and intelligence impairment induced by long-term AC-T. Neuropsychological tests detected eight patients with at least one of four types of deficits; intelligence impairment in four patients, verbal delayed recall impairment in eight, verbal short-term memory disturbance in five, and verbal long-term memory disturbance in six. Two types of verbal memory disturbance (short-term one and long-term one) appeared with double dissociation, suggesting that there may be an independence between the two types of verbal memory system. Older patients were more prone to suffer from these reversible deficits. Moreover, all of the patients who resumed AC-T, showed recurrence of the deficits acutely. These observations should indicate the tight relation between long-term AC-T and neuropsychological deficits.

[Significance of flexed posture and neck instability as a cause of chronic muscle contraction headache].

Cause of a muscle contraction headache (MCH) is due to sustained contraction of the neck and head muscles. This is proved by the effect of local anesthesia and EMG findings. However, the pathophysiology of abnormal muscle contraction is still unclear. Also, there is no explanation about female's greater susceptibility to MCH. The purpose of our report is to study the mechanism of abnormal muscle contraction and to find out a way to prevent it. We have examined 826 (572 female & 254 male) patients with MCH using EMG and dynamic X-ray. Results are most of MCH patients have a tendency to bend their head downward at the onset of headache. EMG shows continuous discharge of the posterior neck muscles so long as they keep this posture. Once they look up, however, EMG discharge usually subsides. Therefore, these muscle contraction are not involuntary, but passive as the results of drooping head. In 12 patients, severe attack of MCH were temporarily alleviated by the local anesthesia to the suboccipital tender point. In patients complaining MCH of one side, they often have a tendency to bend their neck toward the opposite direction, thus contracting the painful side of the neck muscles. It is also found that looking up to make orbito-meatal line more than 10 degrees from horizontal plane is enough to minimize muscle contraction, and to prevent or alleviate headache. Not all people experience headache, though.(ABSTRACT TRUNCATED AT 250 WORDS)

[Muscle contraction headache and posture--with special reference to ischemic contraction of the posterior neck muscles].

Cause of muscle contraction headache (MCH) results from sustained contraction of scalp and posterior neck muscles. Recently, we published an effect of posture on the etiology of MCH. According to our data, head bending posture seems to be one of the main causes of sustained contraction of the posterior neck muscles. Wolff presented a hypothesis of ischemic contraction of these muscles as a cause of pain. However, about the blood flow of scalp or posterior neck muscles, only two reports were published so far. These two papers failed to demonstrate a reduction of blood flow in MCH patients, and neglected the effect of posture. The purpose of this report is to examine a change of blood flow of posterior neck muscles with the change of posture. A total of 40 patients with MCH were studied using laser doppler blood flow meter. Needle shaped probe with a diameter of 0.55 mm was inserted 15 mm into the posterior neck muscle. The angle between orbito-meatal line and horizontal plane were measured using a light helmet with goniometer. Surface EMG of the posterior neck muscles was recorded at the same time. In the case of controls who do not experience headache, the amplitude of EMG increases slightly with the bending posture (40 microV with OM line 20 degrees upward from the horizontal plane, 46 microV with OM line horizontal, and 52 microV when 30 degrees downward). In reverse to the increase of the EMG activity, blood flow of the neck muscles decreases (12 ml/100 g/min with OM line 20 degrees upward, 10.8 with OM line horizontal, 7.6 at 10 degrees down, 4.6 at 20 degrees down, and 4.1 at 30 degrees down).(ABSTRACT TRUNCATED AT 250 WORDS)

[Tension type headache with special reference to muscle abnormality].

Muscle contraction headache (tension-type headache; MCH) usually begins when a patient is looking down or bending their neck. In the case of MCH patients, EMG activity of the posterior neck muscles at a sitting posture is significantly higher than the controls when the orbito-meatal line is horizontal or bending downward. Comparing with the controls, blood flow of the posterior neck muscle decreases sharply when the head is bent downward. Decrease of the muscle blood flow continues if the muscle is passively contracted. However, in the case of active contraction, blood flow recovers reflexly in 30 seconds. This explains why postural muscle contraction is important. When a patient is ordered to bend her neck down at the orbitomeatal line 30 degrees from horizontal, patient complains of a dull feeling at her posterior neck muscles in 30 seconds. In two minutes dull headache appears at the occipital area, soon becoming more intense and spreading to the forehead and temporal area. Once she looks up, muscle contraction of the neck disappears though she still feels headache. After the local anesthesia is applied to the occipital tender point, her headache disappears completely. From this experiment, MCH is a referred pain from occipital tender point which is the insertion point of occipital neck muscles. Patients with poor stability of cervical bone, and relatively heavy head weight compared with their neck are susceptible to MCH. Psychological stress decreases blood flow of the muscle and aggravates ischemic muscle contraction. Other risk factors include hypotension, anemia, and weak muscle power.

[A case of coccidioidomycosis with central nervous system involvement].

We report a 44-year-old Japanese man with chronic meningitis due to coccidoiodomycosis. He was admitted to our hospital because of pneumonia after the business trip to Phoenix, Arizona. Coccidioid immitis was cultured from periathric abscess on the sternoclavicular joint. He became asymptomatic by 5-FC administration. One year later, however, he complained of headache and fever. Coccidiodial meningitis was diagnosed by cerebrospinal fluid (CSF) examination. Both systemic and intrathecal administration of miconazole and oral itraconazole were ineffective. While meningitis was not cured for three years, normal pressure hydrocephalus (NPH) developed. CSF cell count fell into normal range after administration of fluconazole (800 mg/day) for thirteen months, but NPH continued. This is the first report of coccidiodimycosis with CNS involvement in Japan.

[Readiness potential associated with an athetotic movement].

A 28-year-old man was admitted to our hospital because of focal seizures probably generated by the right sensorimotor cortex with secondary generalization for 3 months. He had 5 years history of keratoconjunctivitis and iriditis. Physical examination revealed minimal hemiparesis and hyperreflexia in the left side and left papillitis. Cerebrospinal fluid analysis showed 75 cells per cubic-millimeter (all lymphocytes) and 88 mg/dl protein. Computerized tomography of the brain revealed elimination of the sulcus and vague enhancement of the cortex in the right cerebral hemisphere. The symptoms and the laboratory data improved spontaneously in a few months. Slow, athetotic movements were observed in the left forearm extensor muscles for about 10 days period. Electromyography (EMG) of these movements showed bursts of 300-800 sec in duration which repeated almost regularly at a varying frequency of 0.3-0.5 msec. The electroencephalographic (EEG) studies revealed slow background activities over the right hemisphere. The simultaneous recording of EEGs and EMGs demonstrated no EEG activity correlated with the athetotic movements. In the jerk-locked averaging (JLA) recorded with the time constant of 0.3 sec, no spiky or sharp EEG activities were detected before the EMG discharges of the left forearm extensor muscles. However, JLA with the time constant of 3.2 sec disclosed a slow negative shift which preceded the athetotic movement by about 500 msec. This negative potential was fairly localized in the right central area, which was thought to be consistent with the hand area of the motor cortex contralateral to the muscles showing the athetotic movements. The present case had a wide-spread, mainly unilateral lesion in the cerebral hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

[Recurrent episodic unilateral mydriasis with pleocytosis in the cerebrospinal fluid--a case report].

A 24-year-old female was admitted to our hospital on Aug. 20 in 1986 because of blurred vision and right pupillary dilatation. She had sometimes noticed headache later than 1976, and blurred vision without headache several times a year later than 1983. She had been told her right pupil dilated when she had complained of blurred vision. Neurological examination revealed abnormal findings as follows; diminished sense of smell in the right side, anisocoria (R 8 mm, L 5 mm), bilateral hippus, hypesthesioalgesia in her right face, left trunk and left arm. The pupils were round and contracted promptly to light. Accommodation reflex and ciliospinal reflexes were normal. Neither blepharoptosis nor external ocular muscle paresis were observed. Deep tendon reflexes were normal. Planter responses were flexor. There was no meningeal irritative sign. No abnormal findings were obtained in blood and urine, chest X-p, brain enhanced CT scan, EEG, and cerebral angiography except for slight degree of anemia. Serum TPHA was negative. However, the cell count of cerebrospinal fluid (CSF) was 18/mm3 (Ly 100%) and decreased to 9/mm3 (Ly 100%) in nine days. Protein content and glucose level of CSF were normal. Pupils were not constricted by 0.125% pilocarpine instillation. Loss of smell and sensory disturbance disappeared within three days and her pupils became isocoric by five days after admission. The patients of episodic unilateral mydriasis without apparent cause had relatively same clinical features as "unilateral springing pupil" proposed by Hallett et al. (1970). Except for mydriasis, they had no abnormal findings of neurological and laboratory examinations.(ABSTRACT TRUNCATED AT 250 WORDS)