Diabetes insipidus and cognitive function.

It has been well known that several neuropeptides may affect human behavior, and that some endocrinopathies are associated with impaired higher function of the brain. There have been increasing evidences that vasopressin has both peripheral and central effects, the latter of which is involved in memory. In experimental animals, male mice with a null mutation in the V1a receptor (V1aR) exhibit a profound impairment in social recognition and changes in anxiety-like behavior. An AVP fragment analog has been reported to facilitate memory retention and recall in mice through protein kinase C-independent pathways. In human, a few recent reports have suggested that a familial central diabetes insipidus, caused by a heterozygous mutation in the gene for vasopressin prohormone, have minor disturbances in central nervous system. Taken together, it is hypothesized that the subject with central diabetes insipidus may frequently present with an impaired cognitive ability. It is justified to examine the cognitive function, when we make a diagnosis of central diabetes insipidus and to perform a clinical study to investigate whether central diabetes insipidus may be associated with impairment of higher brain functions.

L-2-hydroxyglutaric aciduria: two Japanese adult cases in one family.

We report two adult Japanese sisters with L-2-hydroxy-glutaric aciduria (acidemia), both of whom were much older (aged 57, 47 years old) than previously reported patients (from neonate to 44 years old), and who presented with differing severity. Magnetic resonance imaging revealed typical subcortical white matter lesions in both cases and showed brainstem atrophy and thickness of the calvarium in the elder sister. L-2-Hydroxyglutaric acid levels were increased in urine, plasma, and cerebrospinal fluid. These cases suggest that organic acid analysis is necessary even in elderly patients who seem to have neurodegenerative disorders.

[Imported trichinellosis with severe myositis--report of a case].

A 38-year-old Japanese male who had traveled in China from September 13 to October 5, 1997, developed fever and severe conjunctivitis from October 20. After he was hospitalized in Kyoto City Hospital for persistent high fever on October 29, he developed muscular weakness and dysphagia which continued for two weeks. An electromyogram showed a myogenic pattern, and laboratory findings showed significant elevation of serum enzyme levels of muscle origin: CPK, 3,095 IU/l; aldorase, 195 IU/l; myoglobin, 7,570 ng/ml, and myoglobinuria, 94,700 ng/ml. The WBC was 10,800/microliter with 45% eosinophils. Muscular biopsy showed degeneration of muscle fibers with infiltration of macrophages and lymphocytes. On further inquiry, it was revealed that the patient had eaten smoked bear meat in China on September 30, three weeks prior to the onset of symptoms. A dot-ELISA serologic test for parasites was positive for Trichinella. Further, a coiled 1.2 mm long Trichinella larve was recovered from approximately 100 mg of frozen biopsied muscle by an enzyme digestion method. Mebendazole was given to the patient at a dosage of 200 mg/day for seven days. CPK levels were normalized within 3 days of the beginning of the treatment, and he was discharged without any symptoms. Physicians must be aware of trichinellosis and should include it in their differential diagnosis when examining patients with myositis and eosinophilia of unknown origin.

Magnetic resonance imaging of skeletal muscles in the polymyositis.

Magnetic resonance imaging of skeletal muscles was performed in 11 patients with polymyositis. Two types of muscle lesions were revealed. The first, inflammation, showed increased signal intensity on T2-weighted images and iso-intensity on T1-weighted images. The second, fatty replacement, showed increased signal intensity on both images. The coronal sections could elucidate the extension of the lesion in each affected muscle. Inflammation was relatively diffuse, while homogeneous fatty replacement tended to begin at the lower myotendinous junctions.

Familial isolated hypoparathyroidism: case report with serum PTHrP examination.

We report a family, with isolated hypoparathyroidism. The proband was a 24-year-old woman, who presented with paresthesia of both hands. She had a mild degree of extrapyramidal signs, such as rigidity and decrease in arm swinging. Laboratory examinations revealed low PTH levels, mild hypocalcemia and hyperphosphatemia in the proband, her father, a younger brother and a younger sister, whereas her mother had normal serum calcium, phosphorus and PTH levels. These results indicate that four members of the family were affected, suggesting autosomal dominant inheritance. Brain CT revealed calcification of basal ganglia in the proband, her father and a younger sister, but not in her younger brother. Serum PTH-related protein (PTHrP) levels were examined, and found to be slightly high only in the father of the proband.

Idiopathic hypertrophic cranial pachymeningitis associated with hydrocephalus and myocarditis: remarkable steriod-induced remission of hypertrophic dura mater.

We describe a patient with idiopathic hypertrophic cranial pachymeningitis (IHCP) associated with hydrocephalus and myocarditis in whom steroids caused remission of the hypertrophic dura and enlarged ventricles. Myocarditis induced complete atrioventricular block that responded to steroids initially but later required permanent pacemaker implantation. Serum ANA and anti-dsDNA antibody were positive. Our case suggests that IHCP and myocarditis may share a common autoimmune etiology.

Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in cortical myoclonus.

Scalp topography of giant SEPs to median nerve stimulation was studied in 4 patients with cortical myoclonus of various etiology. The positive peak (P30) at the contralateral parietal area was simultaneously accompanied by a negative peak at the frontal area (N30), and at least one of these two peaks was enhanced in 2 patients. Another positive peak (P25) and a negative peak (N35) were also identified at the peri-rolandic area with different latency from P30 and N30, respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2 patients. It is concluded that, as seen in normal subjects, tangential (P30-N30) and radial (P25 and N35) components of SEPs are most likely distinguishable in giant SEPs, and that either one or both of those components is enhanced in different ways depending on the patients.

Localized polymyositis associated with chronic thyroiditis.

We describe a case of localized polymyositis accompanied by chronic thyroiditis. Computerized tomogram and magnetic resonance imaging (MRI) studies clearly revealed the lesion localized in the left gastrocnemius muscle. MRI was useful in determining the extent and severity of the muscle lesion. Steroid administration was very effective in the treatment of this patient.

[Effects of insulin-induced hypoglycemia on catecholamine secretion and blood pressure in neurological disorders affecting autonomic nervous system].

The effects of insulin-induced hypoglycemia on catecholamine secretion were investigated in patients with various neurological disorders affecting the autonomic nervous system. In control subjects, insulin-induced hypoglycemia resulted in marked increases in plasma epinephrine and norepinephrine levels. Heart rates were increased within 15 minutes after the insulin injection which were associated with slight elevation and depression of systolic and diastolic blood pressure, respectively. In patients with upper level spinal cord lesions (C1-T6) of various etiology, Shy-Drager syndrome and familial amyloidosis, insulin-induced hypoglycemia failed to increase plasma epinephrine and norepinephrine levels and resulted in falls in systolic and/or diastolic blood pressure 15 minutes after the injection. Heart rates were increased at 30-45 minutes after the injection. In patients with lower spinal cord lesions (T10-L1), neurosyphilis or brain stem tumor with orthostatic hypotension, the catecholamine responses were normal and blood pressure did not fall during insulin-induced hypoglycemia. In patients with Parkinson's disease and spinocerebellar degeneration with autonomic symptoms catecholamine responses were not impaired. These findings suggest that any lesion involving the sympathetic efferent systems of baroreflex such as the spinal descending pathway, sympathetic preganglionic neuron and peripheral nervous system causes both impairment of catecholamine secretion and a fall in blood pressure during hypoglycemia, and that lesions in sympatho-afferent system may not affect the secretion of catecholamine and neural control of blood pressure.

[A case of phenytoin intoxication induced by hypothyroidism].

A 42-year-old woman who presented phenytoin intoxication induced by acute hypothyroidism was reported. She had a 29-year history of hypothyroidism and a 18-year history of epilepsy. She was treated with phenytoin (PHT) 100 mg, mephobarbital (MPB) 200 mg, valproic acid (VPA) 400 mg and thyroid powder 100 mg daily for 2 years. She had no medical problem until she noticed gait disturbance and diplopia which appeared 1 month after sudden withdrawal of thyroid powder. On admission, she was somnolent and somewhat disoriented. She had nystagmus in horizontal direction of gaze. Her speech was slurred and she could not sit nor stand due to trunkal ataxia. There was prominent intentional tremor in finger-nose test and heel-shin test showed severe ataxia. Blood cell count and blood chemistry examinations were normal. Serum PHT, phenobarbital (PB) levels were elevated as to 26.4, 36.4 micrograms/ml, respectively. VPA level was low. The endocrinological examinations revealed primary hypothyroidism. EEG showed generalized slow background, but cranial MRI, EMG, SEP and ECG were normal. Thyroxine (T4) administration was started soon, and in the course of thyroid hormone replacement, her cerebellar symptoms gradually improved and serum PHT level decreased even to the subtherapeutical level with the same amount of antiepileptic drugs treatment. By the 40th day of admission, thyroid function became normal and cerebellar signs disappeared, however, she needed 200 mg PHT daily to obtain good control of epilepsy. Cerebellar symptoms of this patient were thought to be PHT intoxication rather than ataxia caused by hypothyroidism itself from the viewpoint of clinical manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Two brother cases of late-onset familial amyloidotic polyneuropathy in Kyoto].

Measurement of variant Met30 transthyretin is diagnostic for a patients with familial amyloidotic polyneuropathy (FAP) type I. The elder brother first noticed numbness of the feet at 64 years of age, and developed weakness of the legs. A few years later, he noticed numbness of the hands, and he was admitted to the hospital at 67 years of age. He was emaciated and had hoarseness and macroglossia. He had moderate muscle atrophy and weakness of all extremities with distal predominance. Deep tendon reflexes were hypoactive in the upper limbs and absent in the lower limbs. There was marked sensory loss of pain and temperature in all 4 limbs distally, and position sense was also impaired. He had mild orthostatic hypotension, severe cardiomegaly and arrhythmia. The younger brother noticed cold sensation of the feet and sexual impotence at 59 years of age. Two years later, he had numbness of the feet and developed weakness of the legs. At 65 years of age, he was admitted to the hospital because of the micturition syncope. He was emaciated and had macroglossia. He had moderate muscle atrophy and weakness of all extremities with distal predominance. Deep tendon reflexes were absent. There was marked sensory loss in the extremities which was predominant in pain and temperature. He had severe orthostatic hypotension (112/70 mmHg in supine position, 50/30 mmHg on standing). Plasma NE value was low and showed poor response to standing. He had neither cardiomegaly nor arrhythmia. Their parents were supposed to have no neurological symptom and were not related with any other Japanese foci of FAP.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of amphetamine on the in vivo release of dopamine, somatostatin and neuropeptide Y from rat caudate nucleus.

Somatostatin, neuropeptide Y and dopamine release from the conscious rat caudate nucleus were investigated using the push-pull perfusion method. Significant reductions in somatostatin and neuropeptide Y release coincided with increased dopamine release, suggesting that dopamine has an inhibitory effect on the release of both peptides. Changes in the levels of both peptides were positively correlated, consistent with their co-release from neuropeptide Y- and somatostatin-containing striatal neurons.

Subcellular distribution of the immunoreactive peptide histidine isoleucine in the rat brain and release from synaptosomes in vitro.

Subcellular fractionation studies of rat brain homogenate revealed that peptide histidine isoleucine-like immunoreactivity (PHI-LI) was enriched in synaptosomal preparations. PHI-LI was released by high potassium concentrations from synaptosomal pellets incubated in vitro. These results suggest a possible physiological role of PHI in the central nervous system as a neurotransmitter or modulator of synaptic function.

Effect of DN-1417, a synthetic thyrotropin-releasing hormone analogue, on [3H]GABA binding in the cerebellum of ataxic rats.

The neonatal administration of cytocine arabinoside (40 mg/kg, s.c.) induced marked ataxia and hypoplastic cerebellum in male Sprague-Dawley rats. Specific [3H]GABA binding in the cerebellum was significantly reduced by cytosine arabinoside, whereas [3H]GABA binding in the cerebral cortex was not changed. The administration of DN-1417 (1 mg/100 g body wt., i.p.), a synthetic derivative of thyrotropin-releasing hormone (TRH), significantly increased [3H]GABA binding in the cerebellum of cytosine arabinoside-induced ataxic rats. These results suggest that TRH may play a role in regulating GABA receptors involved in the function of the rat cerebellum.

In vivo effects of phenytoin and phenobarbital on GABA receptors in rat cerebral cortex and cerebellum.

The in vivo effects of anticonvulsants on specific binding of [3H]GABA in the rat brain were examined in male Wistar rats. Acute treatment with phenobarbital increased specific [3H]GABA binding in the cerebral cortex, whereas repeated treatment with phenobarbital failed to change [3H]GABA binding. [3H]GABA binding in the cerebellum was not influenced by phenobarbital administration. Acute treatment with phenytoin produced no change in [3H]GABA binding, whereas repeated treatment with phenytoin caused a significant increase in [3H]GABA binding in the cerebellum, but not in the cerebral cortex. The effects of these anticonvulsants may be due, at least in part, to GABA receptor-mediated mechanisms.

Inhibition by DN-1417 (a TRH derivative) of [3H]GABA binding in the rat brain.

The administration of DN-1417, a synthetic derivative of TRH with more potent central action, significantly reduced specific [3H]GABA binding in the cerebellum, whereas [3H]GABA binding in the cerebral cortex was not changed. Scatchard analysis showed that the decreased [3H]GABA binding in the cerebellum was due to decreased binding sites of both high and low affinities. [3H]GABA binding to brain synaptic membranes was not affected by the addition of either TRH or DN-1417 in vitro. These findings suggest that TRH may play a role in regulating GABA receptors in the rat cerebellum.